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    • 1
    • 1
    • 177Lu-DOTA-radioconjugate
    • SSTR2
    • 2 Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Öberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, Krenning E; NETTER-1 Trial Investigators. Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med 2017; 376:125-135.
    • A
    • ABBV-637
    • EGFR
    • 4 Study of Intravenous (IV) ABBV-637 Alone or in Combination With IV Docetaxel/Osimertinib to Assess Adverse Events and Change in Disease Activity in Adult Participants With Relapsed/Refractory (R/R) Solid Tumors [NCT04721015]
    • ABN401
    • MET
    • 4 . . [DOI:]
    • 4 Kim J, Park KE, Jeong YS, Kim Y, Park H, Nam JH, Jung K, Son WS, Jung HS, Lee JH, Jeong SH, Kim NA, Ha JD, Cho SY, Choi YL, Chung SJ, Choi JY, Hong S, Shin YK. Therapeutic Efficacy of ABN401, a Highly Potent and Selective MET Inhibitor, Based on Diagnostic Biomarker Test in MET-Addicted Cancer. Cancers (Basel) 2020; 12(6). pii: E1575.
    • ABT-806
    • EGFR
    • 4 Maron SB, Moya S, Morano F, Emmett MJ, Chou JF, Sabwa S, Walch H, Peterson B, Schrock AB, Zhang L, Janjigian YY, Chalasani S, Ku GY, Disel U, Enzinger P, Uboha N, Kato S, Yoshino T, Shitara K, Nakamura Y, Saeed A, Kasi P, Chao J, Lee J, Capanu M, Wainberg Z, Petty R, Pietrantonio F, Klempner SJ, Catenacci DVT. Epidermal Growth Factor Receptor Inhibition in Epidermal Growth Factor Receptor-Amplified Gastroesophageal Cancer: Retrospective Global Experience. J Clin Oncol 2022 Mar 29:JCO2102453. [Epub ahead of print]
    • AG-270
    • MTAP
    • 4 Gary Kwan Leung Chan, Samantha M. Maisel, Y. Christina Hwang, Rebecca Wolber, Danielle L. Swaney, Nabeel Bardeesy, John D. Gordan. Mapping oncogenic signal transduction in PKA-driven cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 309.
    • AMG 337
    • MET
    • 3 Van Cutsem E, Karaszewska B, Kang YK, Chung HC, Shankaran V, Siena S, Go NF, Yang H, Schupp M, Cunningham D. A Multicenter Phase II Study of AMG 337 in Patients with MET-Amplified Gastric/Gastroesophageal Junction/Esophageal Adenocarcinoma and Other MET-Amplified Solid Tumors. Clin Cancer Res 2019; 25:2414-2423.
    • AMG-596
    • EGFR
    • 4 Rosenthal M, Balana C, Linde MEV, Sayehli C, Fiedler WM, Wermke M, Massard C, Ang A, Kast J, Stienen S, Cloughesy TF. Novel anti-EGFRvIII bispecific T cell engager (BiTE) antibody construct in glioblastoma (GBM): Trial in progress of AMG 596 in patients with recurrent or newly diagnosed disease. J Clin Oncol 2019; 37(15_suppl):
    • 4 Gedeon PC, Choi BD, Hodges TR, Mitchell DA, Bigner DD, Sampson JH. An EGFRvIII-targeted bispecific T-cell engager overcomes limitations of the standard of care for glioblastoma. Expert Rev Clin Pharmacol 2013; 6:375-86.
    • AMG-650
    • TP53
    • 4 Govindan R, Townsend AR, Miller KD, Mehmi I, Kuboki Y, Dumbrava EE, Hamilton EP, Vuu I, Rasmussen E, Mileshkin LR, Genta S, Iwata H, Adams S, Fujii H, Chawla SP, Center R, Monica S, CA . Trial in progress: A phase 1, multicenter, open-label, dose-exploration and dose-expansion study evaluating the safety, tolerability, pharmacokinetics, and efficacy of AMG650 in subjects with advanced solid tumors. J Clin Oncol 2021; 39(15_suppl):
    • 4 Tamayo NA, Bourbeau MP, Allen JR, Ashton KS, Chen JJ, Kaller MR, Nguyen TT, Nishimura N, Pettus LH, Walton M, Belmontes B, Moriguchi J, Chen K, McCarter JD, Hanestad K, Chung G, Ninniri MSS, Sun J, Poppe L, Spahr C, Hui J, Jia L, Wu T, Dahal UP, Edson KZ, Payton M. Targeting the Mitotic Kinesin KIF18A in Chromosomally Unstable Cancers: Hit Optimization Toward an In Vivo Chemical Probe. J Med Chem 2022; 65:4972-4990.
    • AMX-818
    • ERBB2
    • 4 Milton To, Pete Yeung, Michael Fox, Mikhail Hammond, Fiore Cattaruzza, Ayesha Nazeer, Caitlin Koski, Lucas Liu, Sina Khorsand, Deena Rennerfeldt, Kari Morrissey, Zachary Lange, Ming Dong, Sharon Lam, Mika K. Derynck, Bryan A. Irving, Volker Schellenberger. AMX-818, a novel prodrug HER2-XPAT T-cell engager (TCE) with potent T cell activation, proteolytic cleavage and efficacy in xenograft tumors, and wide safety margins in NHP (Non Human Primate) [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P193.
    • ATM inhibitor
    • FANCG
    • 4 Kennedy RD, Chen CC, Stuckert P, Archila EM, De la Vega MA, Moreau LA, Shimamura A, D'Andrea AD. Fanconi anemia pathway-deficient tumor cells are hypersensitive to inhibition of ataxia telangiectasia mutated. J Clin Invest 2007; 117:1440-9.
    • ATR inhibitor
    • FANCM
    • 4 Collis SJ, Ciccia A, Deans AJ, Horejsí Z, Martin JS, Maslen SL, Skehel JM, Elledge SJ, West SC, Boulton SJ. FANCM and FAAP24 function in ATR-mediated checkpoint signaling independently of the Fanconi anemia core complex. Mol Cell 2008; 32:313-24.
    • 4 Schwab RA, Blackford AN, Niedzwiedz W. ATR activation and replication fork restart are defective in FANCM-deficient cells. EMBO J 2010; 29:806-18.
    • 4 Singh TR, Ali AM, Paramasivam M, Pradhan A, Wahengbam K, Seidman MM, Meetei AR. ATR-dependent phosphorylation of FANCM at serine 1045 is essential for FANCM functions. Cancer Res 2013; 73:4300-10.
    • AZD1390 + Radiotherapy
    • ATM
    • 4 Durant ST, Zheng L, Wang Y, Chen K, Zhang L, Zhang T, Yang Z, Riches L, Trinidad AG, Fok JHL, Hunt T, Pike KG, Wilson J, Smith A, Colclough N, Reddy VP, Sykes A, Janefeldt A, Johnström P, Varnäs K, Takano A, Ling S, Orme J, Stott J, Roberts C, Barrett I, Jones G, Roudier M, Pierce A, Allen J, Kahn J, Sule A, Karlin J, Cronin A, Chapman M, Valerie K, Illingworth R, Pass M. The brain-penetrant clinical ATM inhibitor AZD1390 radiosensitizes and improves survival of preclinical brain tumor models. Sci Adv 2018; 4:eaat1719. eCollection 2018 Jun.
    • AZD3463
    • ROS1
    • R2 Davare MA, Vellore NA, Wagner JP, Eide CA, Goodman JR, Drilon A, Deininger MW, O'Hare T, Druker BJ. Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors. Proc Natl Acad Sci U S A 2015; 112:E5381-90.
    • R2 Guisier F, Piton N, Salaun M, Thiberville L. ROS1-rearranged NSCLC With Secondary Resistance Mutation: Case Report and Current Perspectives. Clin Lung Cancer 2019; 20:e593-e596.
    • ROS1
    • 4 Davare MA, Vellore NA, Wagner JP, Eide CA, Goodman JR, Drilon A, Deininger MW, O'Hare T, Druker BJ. Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors. Proc Natl Acad Sci U S A 2015; 112:E5381-90.
    • AZD4547
    • FGFR3
    • R2 Chell V, Balmanno K, Little AS, Wilson M, Andrews S, Blockley L, Hampson M, Gavine PR, Cook SJ. Tumour cell responses to new fibroblast growth factor receptor tyrosine kinase inhibitors and identification of a gatekeeper mutation in FGFR3 as a mechanism of acquired resistance. Oncogene 2013; 32:3059-70.
    • FGFR2
    • R2 Byron SA, Chen H, Wortmann A, Loch D, Gartside MG, Dehkhoda F, Blais SP, Neubert TA, Mohammadi M, Pollock PM. The N550K/H mutations in FGFR2 confer differential resistance to PD173074, dovitinib, and ponatinib ATP-competitive inhibitors. Neoplasia 2013; 15:975-88.
    • R2 Helsten T, Schwaederle M, Kurzrock R. Fibroblast growth factor receptor signaling in hereditary and neoplastic disease: biologic and clinical implications. Cancer Metastasis Rev 2015; 34:479-96.
    • MET
    • R2 Kim SM, Kim H, Yun MR, Kang HN, Pyo KH, Park HJ, Lee JM, Choi HM, Ellinghaus P, Ocker M, Paik S, Kim HR, Cho BC. Activation of the Met kinase confers acquired drug resistance in FGFR-targeted lung cancer therapy. Oncogenesis 2016; 5:e241.
    • R2 Malchers F, Ercanoglu M, Schütte D, Castiglione R, Tischler V, Michels S, Dahmen I, Brägelmann J, Menon R, Heuckmann JM, George J, Ansén S, Sos ML, Soltermann A, Peifer M, Wolf J, Büttner R, Thomas RK. Mechanisms of Primary Drug Resistance in FGFR1-Amplified Lung Cancer. Clin Cancer Res 2017; 23:5527-5536.
    • FGFR1
    • R2 Cowell JK, Qin H, Hu T, Wu Q, Bhole A, Ren M. Mutation in the FGFR1 tyrosine kinase domain or inactivation of PTEN is associated with acquired resistance to FGFR inhibitors in FGFR1-driven leukemia/lymphomas. Int J Cancer 2017; 141:1822-1829.
    • FGFR3
    • R2 Pal SK, Rosenberg JE, Hoffman-Censits JH, Berger R, Quinn DI, Galsky MD, Wolf J, Dittrich C, Keam B, Delord JP, Schellens JHM, Gravis G, Medioni J, Maroto P, Sriuranpong V, Charoentum C, Burris HA, Grünwald V, Petrylak D, Vaishampayan U, Gez E, De Giorgi U, Lee JL, Voortman J, Gupta S, Sharma S, Mortazavi A, Vaughn DJ, Isaacs R, Parker K, Chen X, Yu K, Porter D, Graus Porta D, Bajorin DF. Efficacy of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Inhibitor, in Patients with Previously Treated Advanced Urothelial Carcinoma with FGFR3 Alterations. Cancer Discov 2018; 8:812-821.
    • FGFR1, FGFR3
    • R2 Aggarwal C, Redman MW, Lara PN Jr, Borghaei H, Hoffman P, Bradley JD, Newman AJ 3rd, Feldman MJ, Minichiello K, Miao J, Mack PC, Papadimitrakopoulou VA, Herbst RS, Kelly K, Gandara DR. SWOG S1400D (NCT02965378), a Phase II Study of the Fibroblast Growth Factor Receptor Inhibitor AZD4547 in Previously Treated Patients With Fibroblast Growth Factor Pathway-Activated Stage IV Squamous Cell Lung Cancer (Lung-MAP Substudy). J Thorac Oncol 2019; 14:1847-1852.
    • FGFR1, FGFR2
    • R2 Chae YK, Hong F, Vaklavas C, Cheng HH, Hammerman P, Mitchell EP, Zwiebel JA, Ivy SP, Gray RJ, Li S, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Mansfield A, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of AZD4547 in Patients With Tumors Harboring Aberrations in the FGFR Pathway: Results From the NCI-MATCH Trial (EAY131) Subprotocol W. J Clin Oncol 2020; 38:2407-2417.
    • FGFR2
    • R2 Sootome H, Fujita H, Ito K, Ochiiwa H, Fujioka Y, Ito K, Miura A, Sagara T, Ito S, Ohsawa H, Otsuki S, Funabashi K, Yashiro M, Matsuo K, Yonekura K, Hirai H. Futibatinib Is a Novel Irreversible FGFR 1-4 Inhibitor That Shows Selective Antitumor Activity against FGFR-Deregulated Tumors. Cancer Res 2020; 80:4986-4997.
    • FGFR1, FGFR3
    • R2 Redman MW, Papadimitrakopoulou VA, Minichiello K, Hirsch FR, Mack PC, Schwartz LH, Vokes E, Ramalingam S, Leighl N, Bradley J, Miao J, Moon J, Highleyman L, Miwa C, LeBlanc ML, Malik S, Miller VA, Sigal EV, Adam S, Wholley D, Sigman C, Smolich B, Blanke CD, Kelly K, Gandara DR, Herbst RS. Biomarker-driven therapies for previously treated squamous non-small-cell lung cancer (Lung-MAP SWOG S1400): a biomarker-driven master protocol. Lancet Oncol 2020 Oct 27. pii: S1470-2045(20)30475-7. [Epub ahead of print]
    • FGFR2
    • 4 Smyth EC, Turner NC, Peckitt C, Pearson A, Brown G, Chua S, Gillbanks A, Johnston SRD, TARAZONA N, Cutts R, Kilgour E, Rooney C, Smith NR, Sumpter KA, Ajaz MA, Thomas AL, Watkins D, Chau I, Popat S, Cunningham D. Phase II multicenter proof of concept study of AZD4547 in FGFR amplified tumours. J Clin Oncol 2015; 33(15_suppl): 2508-2508.
    • FGFR1, FGFR2, FGFR3
    • 4 Chae YK, Vaklavas C, Cheng HH, Hong F, Harris L, Mitchell EP, Zwiebel JA, McShane L, Gray RJ, Li S, Ivy SP, Ansher SS, Hamilton SR, Williams PM, Tricoli JV, Arteaga CL, Conley BA, O'Dwyer PJ, Chen AP, Flaherty K, MA HBMMGHB. Molecular analysis for therapy choice (MATCH) arm W: Phase II study of AZD4547 in patients with tumors with aberrations in the FGFR pathway. J Clin Oncol 2018; 36(15_suppl): 2503-2503.
    • FGFR1
    • 4 Paik PK, Shen R, Ferry D, Soria J, Mathewson A, Kilgour E, Landers D, Frewer P, Brooks N, Andre F. A phase 1b open-label multicenter study of AZD4547 in patients with advanced squamous cell lung cancers: Preliminary antitumor activity and pharmacodynamic data. J Clin Oncol 2014; 32(15_suppl): 8035-8035.
    • FGFR2
    • 4 Van Cutsem E, Bang YJ, Mansoor W, Petty RD, Chao Y, Cunningham D, Ferry DR, Smith NR, Frewer P, Ratnayake J, Stockman PK, Kilgour E, Landers D. A randomized, open-label study of the efficacy and safety of AZD4547 monotherapy versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2 polysomy or gene amplification. Ann Oncol 2017; 28:1316-1324.
    • FGFR1, FGFR3
    • 4 Chae YK, Hong F, Vaklavas C, Cheng HH, Hammerman P, Mitchell EP, Zwiebel JA, Ivy SP, Gray RJ, Li S, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Mansfield A, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of AZD4547 in Patients With Tumors Harboring Aberrations in the FGFR Pathway: Results From the NCI-MATCH Trial (EAY131) Subprotocol W. J Clin Oncol 2020; 38:2407-2417.
    • AZD8055
    • EIF1AX, EIF1AX+NRAS
    • 4 Krishnamoorthy GP, Davidson NR, Leach SD, Zhao Z, Lowe SW, Lee G, Landa I, Nagarajah J, Saqcena M, Singh K, Wendel HG, Dogan S, Tamarapu PP, Blenis J, Ghossein RA, Knauf JA, Rätsch G, Fagin JA. EIF1AX and RAS Mutations Cooperate to Drive Thyroid Tumorigenesis through ATF4 and c-MYC. Cancer Discov 2019; 9:264-281.
    • AZD8055 + JQ1
    • EIF1AX, EIF1AX+NRAS
    • 4 Krishnamoorthy GP, Davidson NR, Leach SD, Zhao Z, Lowe SW, Lee G, Landa I, Nagarajah J, Saqcena M, Singh K, Wendel HG, Dogan S, Tamarapu PP, Blenis J, Ghossein RA, Knauf JA, Rätsch G, Fagin JA. EIF1AX and RAS Mutations Cooperate to Drive Thyroid Tumorigenesis through ATF4 and c-MYC. Cancer Discov 2019; 9:264-281.
    • AZD8055 + Trametinib
    • EIF1AX, EIF1AX+NRAS
    • 4 Krishnamoorthy GP, Davidson NR, Leach SD, Zhao Z, Lowe SW, Lee G, Landa I, Nagarajah J, Saqcena M, Singh K, Wendel HG, Dogan S, Tamarapu PP, Blenis J, Ghossein RA, Knauf JA, Rätsch G, Fagin JA. EIF1AX and RAS Mutations Cooperate to Drive Thyroid Tumorigenesis through ATF4 and c-MYC. Cancer Discov 2019; 9:264-281.
    • AZD8186
    • PTEN
    • 4 Nicci Owusu-Brackett, Ming Zhao, Argun Akcakanat, Kurt W. Evans, Erkan Yuca, Funda Meric-Bernstam. Efficacy of PI3Kβ inhibitor AZD8186 in PTEN-deficient triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5802.
    • AZD9496
    • ESR1
    • 4 Hamilton EP, Patel MR, Armstrong AC, Baird RD, Jhaveri K, Hoch M, Klinowska T, Lindemann JPO, Morgan SR, Schiavon G, Weir HM, Im SA. A First-in-Human Study of the New Oral Selective Estrogen Receptor Degrader AZD9496 for ER+/HER2- Advanced Breast Cancer. Clin Cancer Res 2018; 24:3510-3518.
    • AZD9833
    • ESR1
    • 4 Kingston B, Pearson A, Herrera-Abreu MT, Cutts R, Moretti L, Kilburn L, Johnson H, MacPherson IR, Ring AE, Bliss J, Katzenellenbogen JA, Turner NC. ESR1 F404 mutations and acquired resistance to fulvestrant in the plasmaMATCH study. J Clin Oncol 2022; 40(16_suppl): 1009-1009.
    • Abemaciclib
    • RB1
    • R2 Safonov AM, Bandlamudi C, Selenica P, Marra A, Ferraro E, Mandelker D, Solit DB, Berger MF, Norton L, Powell SN, Shen R, Robson ME, Chandarlapaty S, Reis-Filho JS, Razavi P. Allelic dosage of RB1 drives CDK4/6 inhibitor treatment resistance in metastatic breast cancer. J Clin Oncol 2022; 40(16_suppl): 1010-1010.
    • CDK6
    • R2 Yang C, Li Z, Bhatt T, Dickler M, Giri D, Scaltriti M, Baselga J, Rosen N, Chandarlapaty S. Acquired CDK6 amplification promotes breast cancer resistance to CDK4/6 inhibitors and loss of ER signaling and dependence. Oncogene 2017; 36:2255-2264.
    • RB1
    • R2 O'Leary B, Cutts RJ, Liu Y, Hrebien S, Huang X, Fenwick K, André F, Loibl S, Loi S, Garcia-Murillas I, Cristofanilli M, Huang Bartlett C, Turner NC. The Genetic Landscape and Clonal Evolution of Breast Cancer Resistance to Palbociclib plus Fulvestrant in the PALOMA-3 Trial. Cancer Discov 2018; 8:1390-1403.
    • FAT1
    • R2 Li Z, Razavi P, Li Q, Toy W, Liu B, Ping C, Hsieh W, Sanchez-Vega F, Brown DN, Da Cruz Paula AF, Morris L, Selenica P, Eichenberger E, Shen R, Schultz N, Rosen N, Scaltriti M, Brogi E, Baselga J, Reis-Filho JS, Chandarlapaty S. Loss of the FAT1 Tumor Suppressor Promotes Resistance to CDK4/6 Inhibitors via the Hippo Pathway. Cancer Cell 2018; 34:893-905.e8.
    • CCNE1
    • R2 Turner NC, Liu Y, Zhu Z, Loi S, Colleoni M, Loibl S, DeMichele A, Harbeck N, André F, Bayar MA, Michiels S, Zhang Z, Giorgetti C, Arnedos M, Huang Bartlett C, Cristofanilli M. Cyclin E1 Expression and Palbociclib Efficacy in Previously Treated Hormone Receptor-Positive Metastatic Breast Cancer. J Clin Oncol 2019; 37:1169-1178.
    • CDKN2A
    • 3 Fennell DA, King A, Mohammed S, Greystoke A, Anthony S, Poile C, Nusrat N, Scotland M, Bhundia V, Branson A, Brookes C, Darlison L, Dawson AG, Gaba A, Hutka M, Morgan B, Bajaj A, Richards C, Wells-Jordan P, Thomas A; MiST2 study group. Abemaciclib in patients with p16ink4A-deficient mesothelioma (MiST2): a single-arm, open-label, phase 2 trial. Lancet Oncol 2022 Feb 11. pii: S1470-2045(22)00062-6. [Epub ahead of print]
    • CCND2, CCND3
    • 4 Xueqian Gong, Li-Chun Chio, MaryJo Lallena, Farhana Merzoug, Shaoyou Chu, Yue Webster, Jack Dempsey, Xiwen Ma, Alfonso De Dios, Richard Beckman, Sean G. Buchanan. Molecular features that determine the sensitivity of cancer cells to abemaciclib, an inhibitor of CDK4 and CDK6. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3104. doi:10.1158/1538-7445.AM2015-3104
    • CDKN2A
    • 4 Patnaik A, Rosen LS, Tolaney SM, Tolcher AW, Goldman JW, Gandhi L, Papadopoulos KP, Beeram M, Rasco DW, Hilton JF, Nasir A, Beckmann RP, Schade AE, Fulford AD, Nguyen TS, Martinez R, Kulanthaivel P, Li LQ, Frenzel M, Cronier DM, Chan EM, Flaherty KT, Wen PY, Shapiro GI. Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid Tumors. Cancer Discov 2016; 6:740-53.
    • 4 Gopalan PK, Villegas AG, Cao C, Pinder-Schenck M, Chiappori A, Hou W, Zajac-Kaye M, Ivey AM, Kaye FJ. CDK4/6 inhibition stabilizes disease in patients with p16-null non-small cell lung cancer and is synergistic with mTOR inhibition. Oncotarget 2018; 9:37352-37366. eCollection 2018 Dec 21.
    • Abemaciclib + Anastrazole
    • ERBB2+ESR1
    • 1 Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. J Clin Oncol 2017; 35:3638-3646.
    • Abemaciclib + Fulvestrant
    • ESR1+ERBB2
    • 1 Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Frenzel M, Lin Y, Barriga S, Smith IC, Bourayou N, Llombart-Cussac A. MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. J Clin Oncol 2017; 35:2875-2884.
    • Abemaciclib + Letrozole
    • ERBB2+ESR1
    • 1 Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. J Clin Oncol 2017; 35:3638-3646.
    • Abiraterone Acetate + Goserelin
    • AR
    • 3 Locati LD, Cavalieri S, Bergamini C, Resteghini C, Colombo E, Calareso G, Mariani L, Quattrone P, Alfieri S, Bossi P, Platini F, Capone I, Licitra L. Abiraterone Acetate in Patients With Castration-Resistant, Androgen Receptor-Expressing Salivary Gland Cancer: A Phase II Trial. J Clin Oncol 2021 Oct 1:JCO2100468. [Epub ahead of print]
    • Abiraterone Acetate + Leuprorelin
    • AR
    • 3 Locati LD, Cavalieri S, Bergamini C, Resteghini C, Colombo E, Calareso G, Mariani L, Quattrone P, Alfieri S, Bossi P, Platini F, Capone I, Licitra L. Abiraterone Acetate in Patients With Castration-Resistant, Androgen Receptor-Expressing Salivary Gland Cancer: A Phase II Trial. J Clin Oncol 2021 Oct 1:JCO2100468. [Epub ahead of print]
    • Abiraterone Acetate + Triptorelin
    • AR
    • 3 Locati LD, Cavalieri S, Bergamini C, Resteghini C, Colombo E, Calareso G, Mariani L, Quattrone P, Alfieri S, Bossi P, Platini F, Capone I, Licitra L. Abiraterone Acetate in Patients With Castration-Resistant, Androgen Receptor-Expressing Salivary Gland Cancer: A Phase II Trial. J Clin Oncol 2021 Oct 1:JCO2100468. [Epub ahead of print]
    • Abiraterone acetate
    • AR
    • R2 Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, Chen Y, Mohammad TA, Chen Y, Fedor HL, Lotan TL, Zheng Q, De Marzo AM, Isaacs JT, Isaacs WB, Nadal R, Paller CJ, Denmeade SR, Carducci MA, Eisenberger MA, Luo J. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 2014; 371:1028-38.
    • Adagrasib
    • ALK, BRAF, EGFR, FGFR3, KRAS, MAP2K1, MET, NF1, NRAS, PIK3CA, PIK3R1, PTEN, RAF1, RET, RIT1
    • R2 Awad MM, Liu S, Rybkin II, Arbour KC, Dilly J, Zhu VW, Johnson ML, Heist RS, Patil T, Riely GJ, Jacobson JO, Yang X, Persky NS, Root DE, Lowder KE, Feng H, Zhang SS, Haigis KM, Hung YP, Sholl LM, Wolpin BM, Wiese J, Christiansen J, Lee J, Schrock AB, Lim LP, Garg K, Li M, Engstrom LD, Waters L, Lawson JD, Olson P, Lito P, Ou SI, Christensen JG, Jänne PA, Aguirre AJ. Acquired Resistance to KRASG12C Inhibition in Cancer. N Engl J Med 2021; 384:2382-2393.
    • KRAS
    • 2 Jänne PA, Riely GJ, Gadgeel SM, Heist RS, Ou SI, Pacheco JM, Johnson ML, Sabari JK, Leventakos K, Yau E, Bazhenova L, Negrao MV, Pennell NA, Zhang J, Anderes K, Der-Torossian H, Kheoh T, Velastegui K, Yan X, Christensen JG, Chao RC, Spira AI. Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRASG12C Mutation. N Engl J Med 2022 Jun 3. [Epub ahead of print]
    • KRAS
    • 3 Jänne P, Rybkin I, Spira A, Riely G, Papadopoulos K, Sabari J, Johnson M, Heist R, Bazhenova L, Barve M, Pacheco J, Leal T, Velastegui K, Cornelius C, Olson P, Christensen J, Kheoh T, Chao R, Ou S. KRYSTAL-1: Activity and Safety of Adagrasib (MRTX849) in Advanced/ Metastatic Non–Small-Cell Lung Cancer (NSCLC) Harboring KRAS G12C Mutation. E J Cancer 2020; 138 (2): S1. 10.1016/S0959-8049(20)31076-5
    • 3 Ou SI, Jänne PA, Leal TA, Rybkin II, Sabari JK, Barve MA, Bazhenova LA, Johnson ML, Velastegui KL, Cilliers C, Christensen JG, Yan X, Chao RC, Papadopoulos KP. First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRASG12C Solid Tumors (KRYSTAL-1). J Clin Oncol 2022 Feb 15:JCO2102752. [Epub ahead of print]
    • KRAS+STK11
    • KRAS
    • 4 Ou SI, Jänne PA, Leal TA, Rybkin II, Sabari JK, Barve MA, Bazhenova LA, Johnson ML, Velastegui KL, Cilliers C, Christensen JG, Yan X, Chao RC, Papadopoulos KP. First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRASG12C Solid Tumors (KRYSTAL-1). J Clin Oncol 2022 Feb 15:JCO2102752. [Epub ahead of print]
    • Adagrasib + Cetuximab
    • KRAS
    • Adavosertib
    • TP53
    • 3 Liu JF, Xiong N, Campos SM, Wright AA, Krasner C, Schumer S, Horowitz N, Veneris J, Tayob N, Morrissey S, West G, Quinn R, Matulonis UA, Konstantinopoulos PA. Phase II Study of the WEE1 Inhibitor Adavosertib in Recurrent Uterine Serous Carcinoma. J Clin Oncol 2021 Mar 11:JCO2003167. [Epub ahead of print]
    • TP53+KRAS
    • 3 Seligmann JF, Fisher DJ, Brown LC, Adams RA, Graham J, Quirke P, Richman SD, Butler R, Domingo E, Blake A, Yates E, Braun M, Collinson F, Jones R, Brown E, de Winton E, Humphrey TC, Parmar M, Kaplan R, Wilson RH, Seymour M, Maughan TS; FOCUS4 Trial Investigators. Inhibition of WEE1 Is Effective in TP53- and RAS-Mutant Metastatic Colorectal Cancer: A Randomized Trial (FOCUS4-C) Comparing Adavosertib (AZD1775) With Active Monitoring. J Clin Oncol 2021; 39:3705-3715.
    • CCNE1
    • 4 Chen X, Low KH, Alexander A, Jiang Y, Karakas C, Hess KR, Carey JPW, Bui TN, Vijayaraghavan S, Evans KW, Yi M, Ellis DC, Cheung KL, Ellis IO, Fu S, Meric-Bernstam F, Hunt KK, Keyomarsi K. Cyclin E Overexpression Sensitizes Triple-Negative Breast Cancer to Wee1 Kinase Inhibition. Clin Cancer Res 2018; 24:6594-6610.
    • ATRX
    • 4 Liang J, Zhao H, Diplas BH, Liu S, Liu J, Wang D, Lu Y, Zhu Q, Wu J, Wang W, Yan H, Zeng YX, Wang X, Jiao Y. Genome-Wide CRISPR-Cas9 Screen Reveals Selective Vulnerability of ATRX-Mutant Cancers to WEE1 Inhibition. Cancer Res 2020; 80:510-523.
    • Ado-Trastuzumab Emtansine
    • ERBB2
    • R2 Yu DH, Tang L, Dong H, Dong Z, Zhang L, Fu J, Su X, Zhang T, Fu H, Han L, Xie L, Chen H, Qian Z, Zhu G, Wang J, Ye Q, Zhang J, Yin X, Zhang X, Ji J, Ji Q. Oncogenic HER2 fusions in gastric cancer. J Transl Med 2015; 13:116.
    • R2 Xu X, De Angelis C, Burke KA, Nardone A, Hu H, Qin L, Veeraraghavan J, Sethunath V, Heiser LM, Wang N, Ng CKY, Chen ES, Renwick A, Wang T, Nanda S, Shea M, Mitchell T, Rajendran M, Waters I, Zabransky DJ, Scott KL, Gutierrez C, Nagi C, Geyer FC, Chamness GC, Park BH, Shaw CA, Hilsenbeck SG, Rimawi MF, Gray JW, Weigelt B, Reis-Filho JS, Osborne CK, Schiff R. HER2 Reactivation through Acquisition of the HER2 L755S Mutation as a Mechanism of Acquired Resistance to HER2-targeted Therapy in HER2+ Breast Cancer. Clin Cancer Res 2017; 23:5123-5134.
    • ERBB2
    • 1 Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K; EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012; 367:1783-91.
    • 1 Krop IE, Kim SB, González-Martín A, LoRusso PM, Ferrero JM, Smitt M, Yu R, Leung AC, Wildiers H; TH3RESA study collaborators. Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol 2014; 15:689-99.
    • 1 Krop IE, Kim SB, Martin AG, LoRusso PM, Ferrero JM, Badovinac-Crnjevic T, Hoersch S, Smitt M, Wildiers H. Trastuzumab emtansine versus treatment of physician's choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial. Lancet Oncol 2017; 18:743-754.
    • ERBB2
    • 3 Li BT, Shen R, Offin M, Buonocore DJ, Myers ML, Venkatesh A, Razavi P, Ginsberg MS, Ulaner GA, Solit DB, Hyman DM, Rudin CM, Gedvilaite E, Tsui D, Arcila ME, Kris MG, Weitsman G, Ng T, Scaltriti M, Ho AL. Ado-trastuzumab emtansine in patients with HER2 amplified salivary gland cancers (SGCs): Results from a phase II basket trial. J Clin Oncol 2019; 37(15_suppl): 6001-6001.
    • 3 Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol 2017; 18:640-653.
    • 3 Li BT, Shen R, Buonocore D, Olah ZT, Ni A, Ginsberg MS, Ulaner GA, Offin M, Feldman D, Hembrough T, Cecchi F, Schwartz S, Pavlakis N, Clarke S, Won HH, Brzostowski EB, Riely GJ, Solit DB, Hyman DM, Drilon A, Rudin CM, Berger MF, Baselga J, Scaltriti M, Arcila ME, Kris MG. Ado-Trastuzumab Emtansine for Patients With HER2-Mutant Lung Cancers: Results From a Phase II Basket Trial. J Clin Oncol 2018; 36:2532-2537.
    • 3 Peters S, Stahel R, Bubendorf L, Bonomi P, Villegas A, Kowalski DM, Baik CS, Isla D, Carpeno JC, Garrido P, Rittmeyer A, Tiseo M, Meyenberg C, de Haas S, Lam LH, Lu MW, Stinchcombe TE. Trastuzumab Emtansine (T-DM1) in Patients with Previously Treated HER2-Overexpressing Metastatic Non-Small Cell Lung Cancer: Efficacy, Safety, and Biomarkers. Clin Cancer Res 2019; 25:64-72.
    • ERBB2
    • 4 Jamunarani Veeraraghavan, Ragini Mistry, Sarmistha Nanda, Vidyalakshmi Sethunath, Martin Shea, Tamika Mitchell, Meenakshi Anurag, Michael A. Mancini, Fabio Stossi, C. Kent Osborne, Mothaffar F. Rimawi, Rachel Schiff. HER2 L755S mutation is acquired upon resistance to lapatinib and neratinib and confers cross-resistance to tucatinib and trastuzumab in HER2-positive breast cancer cell models [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD3-09.
    • 4 Jia Z, Liang N, Wang Y, Wang Y, Ye J, Wang W, Li B, Han-Zhang H, Zhao J, Zhang X, Peng F, Chen F, Chen X, Lu Y, Ying S, Dp W, Zhang X, Ma C, Lai L, Ma S, Institute UCH&, Tianjin , Center CXAR, Beijing , XtalPi C, Shenzhen , China . Clinical management of lung adenocarcinoma patients with HER2 V659E mutation. J Clin Oncol 2020; 38(15_suppl):
    • 4 Yu DH, Tang L, Dong H, Dong Z, Zhang L, Fu J, Su X, Zhang T, Fu H, Han L, Xie L, Chen H, Qian Z, Zhu G, Wang J, Ye Q, Zhang J, Yin X, Zhang X, Ji J, Ji Q. Oncogenic HER2 fusions in gastric cancer. J Transl Med 2015; 13:116.
    • ERBB2+KRAS
    • 4 Sandhu J, Wang C, Fakih M. Clinical Response to T-DM1 in HER2-Amplified, KRAS-Mutated Metastatic Colorectal Cancer. J Natl Compr Canc Netw 2020; 18:116-119.
    • ERBB2
    • 4 Haslem DS, Ji HP, Ford JM, Nadauld LD. Precision Oncology Strategy in Trastuzumab-Resistant Human Epidermal Growth Factor Receptor 2-Positive Colon Cancer: Case Report of Durable Response to Ado-Trastuzumab Emtansine. JCO Precis Oncol 2017; 1. pii: PO.16.00055. eCollection 2017.
    • Ado-Trastuzumab Emtansine + Pertuzumab
    • ERBB2
    • R2 Sartore-Bianchi A, Lonardi S, Martino C, Fenocchio E, Tosi F, Ghezzi S, Leone F, Bergamo F, Zagonel V, Ciardiello F, Ardizzoni A, Amatu A, Bencardino K, Valtorta E, Grassi E, Torri V, Bonoldi E, Sapino A, Vanzulli A, Regge D, Cappello G, Bardelli A, Trusolino L, Marsoni S, Siena S. Pertuzumab and trastuzumab emtansine in patients with HER2-amplified metastatic colorectal cancer: the phase II HERACLES-B trial. ESMO Open 2020; 5:e000911.
    • Afatinib
    • EGFR
    • R1 Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong KK, Meyerson M, Eck MJ. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A 2008; 105:2070-5.
    • R1 Yasuda H, Kobayashi S, Costa DB. EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications. Lancet Oncol 2012; 13:e23-31.
    • EGFR
    • R2 Kwak EL, Shapiro GI, Cohen SM, Becerra CR, Lenz HJ, Cheng WF, Su WC, Robohn M, Le Maulf F, Lobmeyer MT, Chand VK, Iafrate AJ. Phase 2 trial of afatinib, an ErbB family blocker, in solid tumors genetically screened for target activation. Cancer 2013; 119:3043-51.
    • R2 Yasuda H, Park E, Yun CH, Sng NJ, Lucena-Araujo AR, Yeo WL, Huberman MS, Cohen DW, Nakayama S, Ishioka K, Yamaguchi N, Hanna M, Oxnard GR, Lathan CS, Moran T, Sequist LV, Chaft JE, Riely GJ, Arcila ME, Soo RA, Meyerson M, Eck MJ, Kobayashi SS, Costa DB. Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer. Sci Transl Med 2013; 5:216ra177.
    • R2 Matsushima S, Ohtsuka K, Ohnishi H, Fujiwara M, Nakamura H, Morii T, Kishino T, Goto H, Watanabe T. V843I, a lung cancer predisposing EGFR mutation, is responsible for resistance to EGFR tyrosine kinase inhibitors. J Thorac Oncol 2014; 9:1377-84.
    • KRAS
    • R2 Hickish T, Cassidy J, Propper D, Chau I, Falk S, Ford H, Iveson T, Braun M, Potter V, Macpherson IR, Finnigan H, Lee C, Jones H, Harrison M. A randomised, open-label phase II trial of afatinib versus cetuximab in patients with metastatic colorectal cancer. Eur J Cancer 2014; 50:3136-44.
    • EGFR+RB1
    • R2 Niederst MJ, Sequist LV, Poirier JT, Mermel CH, Lockerman EL, Garcia AR, Katayama R, Costa C, Ross KN, Moran T, Howe E, Fulton LE, Mulvey HE, Bernardo LA, Mohamoud F, Miyoshi N, VanderLaan PA, Costa DB, Jänne PA, Borger DR, Ramaswamy S, Shioda T, Iafrate AJ, Getz G, Rudin CM, Mino-Kenudson M, Engelman JA. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat Commun 2015; 6:6377.
    • EGFR+ROS1
    • R2 Zeng L, Yang N, Zhang Y. GOPC-ROS1 Rearrangement as an Acquired Resistance Mechanism to Osimertinib and Responding to Crizotinib Combined Treatments in Lung Adenocarcinoma. J Thorac Oncol 2018; 13:e114-e116.
    • EGFR+RET
    • R2 Piotrowska Z, Isozaki H, Lennerz JK, Gainor JF, Lennes IT, Zhu VW, Marcoux N, Banwait MK, Digumarthy SR, Su W, Yoda S, Riley AK, Nangia V, Lin JJ, Nagy RJ, Lanman RB, Dias-Santagata D, Mino-Kenudson M, Iafrate AJ, Heist RS, Shaw AT, Evans EK, Clifford C, Ou SI, Wolf B, Hata AN, Sequist LV. Landscape of Acquired Resistance to Osimertinib in EGFR-Mutant NSCLC and Clinical Validation of Combined EGFR and RET Inhibition with Osimertinib and BLU-667 for Acquired RET Fusion. Cancer Discov 2018; 8:1529-1539.
    • EGFR+RB1, EGFR+TP53
    • R2 Marcoux N, Gettinger SN, O'Kane G, Arbour KC, Neal JW, Husain H, Evans TL, Brahmer JR, Muzikansky A, Bonomi PD, Del Prete S, Wurtz A, Farago AF, Dias-Santagata D, Mino-Kenudson M, Reckamp KL, Yu HA, Wakelee HA, Shepherd FA, Piotrowska Z, Sequist LV. EGFR-Mutant Adenocarcinomas That Transform to Small-Cell Lung Cancer and Other Neuroendocrine Carcinomas: Clinical Outcomes. J Clin Oncol 2019; 37:278-285.
    • MET
    • R2 Lai GGY, Lim TH, Lim J, Liew PJR, Kwang XL, Nahar R, Aung ZW, Takano A, Lee YY, Lau DPX, Tan GS, Tan SH, Tan WL, Ang MK, Toh CK, Tan BS, Devanand A, Too CW, Gogna A, Ong BH, Koh TPT, Kanesvaran R, Ng QS, Jain A, Rajasekaran T, Yuan J, Lim TKH, Lim AST, Hillmer AM, Lim WT, Iyer NG, Tam WL, Zhai W, Tan EH, Tan DSW. Clonal MET Amplification as a Determinant of Tyrosine Kinase Inhibitor Resistance in Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer. J Clin Oncol 2019; 37:876-884.
    • EGFR+ALK, EGFR+RET
    • R2 Offin M, Somwar R, Rekhtman N, Benayed R, Chang JC, Plodkowski A, Lui AJW, Eng J, Rosenblum M, Li BT, Riely GJ, Rudin CM, Kris MG, Travis W, Drilon A, Arcila ME, Ladanyi M, Yu HA. Acquired ALK and RET Gene Fusions as Mechanisms of Resistance to Osimertinib in EGFR-Mutant Lung Cancers. JCO Precis Oncol 2018;2.
    • ERBB2
    • R2 Robichaux JP, Elamin YY, Vijayan RSK, Nilsson MB, Hu L, He J, Zhang F, Pisegna M, Poteete A, Sun H, Li S, Chen T, Han H, Negrao MV, Ahnert JR, Diao L, Wang J, Le X, Meric-Bernstam F, Routbort M, Roeck B, Yang Z, Raymond VM, Lanman RB, Frampton GM, Miller VA, Schrock AB, Albacker LA, Wong KK, Cross JB, Heymach JV. Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 Activity. Cancer Cell 2019; 36:444-457.e7.
    • EGFR
    • R2 Zhu C, Zhuang W, Chen L, Yang W, Ou WB. Frontiers of ctDNA, targeted therapies, and immunotherapy in non-small-cell lung cancer. Transl Lung Cancer Res 2020; 9:111-138.
    • R2 Qin Y, Jian H, Tong X, Wu X, Wang F, Shao YW, Zhao X. Variability of EGFR exon 20 insertions in 24 468 Chinese lung cancer patients and their divergent responses to EGFR inhibitors. Mol Oncol 2020; 14:1695-1704.
    • R2 Nishino M, Suda K, Koga T, Ohara S, Fujino T, Soh J, Tirunagaru V, Vellanki A, Doebele RC, Mitsudomi T. Activity of tarloxotinib-E in cells with EGFR exon-20 insertion mutations and mechanisms of acquired resistance. Thorac Cancer 2021; 12:1511-1516.
    • R2 Lee C, Kim M, Kim DW, Kim TM, Kim S, Im SW, Jeon YK, Keam B, Ku JL, Heo DS. Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non-Small Cell Lung Cancer. Cancer Res Treat 2021 May 3. [Epub ahead of print]
    • R2 Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 2021; 597:732-737.
    • ERBB2
    • R2 Koga T, Suda K, Nishino M, Fujino T, Ohara S, Hamada A, Soh J, Tirunagaru V, Vellanki A, Doebele RC, Mitsudomi T. Activity and mechanism of acquired resistance to tarloxotinib in HER2 mutant lung cancer: an in vitro study. Transl Lung Cancer Res 2021; 10:3659-3670.
    • EGFR
    • 1 Yang JC, Shih JY, Su WC, Hsia TC, Tsai CM, Ou SH, Yu CJ, Chang GC, Ho CL, Sequist LV, Dudek AZ, Shahidi M, Cong XJ, Lorence RM, Yang PC, Miller VA. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol 2012; 13:539-48.
    • 1 Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 2013; 31:3327-34.
    • 1 Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol 2014; 15:213-22.
    • 1 Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, Shi Y, Kim SW, Laskin J, Kim DW, Arvis CD, Kölbeck K, Laurie SA, Tsai CM, Shahidi M, Kim M, Massey D, Zazulina V, Paz-Ares L. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol 2016; 17:577-89.
    • EGFR
    • 2 Gergis C, Rangachari D, Fujii M, Varkaris A, VanderLaan PA, Kobayashi S, Costa DB. EGFR-A763_Y764insFQEA: A unique exon 20 insertion mutation that displays sensitivity to all classes of approved lung cancer EGFR tyrosine kinase inhibitors. J Clin Oncol 2019; 37(15_suppl):
    • 2 Costa DB. Kinase inhibitor-responsive genotypes in EGFR mutated lung adenocarcinomas: moving past common point mutations or indels into uncommon kinase domain duplications and rearrangements. Transl Lung Cancer Res 2016; 5:331-7.
    • ERBB2
    • 3 Zhao S, Fang W, Pan H, Yang Y, Liang Y, Yang L, Dong X, Zhan J, Wang K, Zhang L. Conformational Landscapes of HER2 Exon 20 Insertions Explain Their Sensitivity to Kinase Inhibitors in Lung Adenocarcinoma. J Thorac Oncol 2020; 15:962-972.
    • ERBB2
    • 4 Jia Z, Liang N, Wang Y, Wang Y, Ye J, Wang W, Li B, Han-Zhang H, Zhao J, Zhang X, Peng F, Chen F, Chen X, Lu Y, Ying S, Dp W, Zhang X, Ma C, Lai L, Ma S, Institute UCH&, Tianjin , Center CXAR, Beijing , XtalPi C, Shenzhen , China . Clinical management of lung adenocarcinoma patients with HER2 V659E mutation. J Clin Oncol 2020; 38(15_suppl):
    • NRG1
    • EGFR
    • 4 Ozer BH, Wiepz GJ, Bertics PJ. Activity and cellular localization of an oncogenic glioblastoma multiforme-associated EGF receptor mutant possessing a duplicated kinase domain. Oncogene 2010; 29:855-64.
    • ERBB2
    • 4 De Grève J, Teugels E, Geers C, Decoster L, Galdermans D, De Mey J, Everaert H, Umelo I, In't Veld P, Schallier D. Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu. Lung Cancer 2012; 76:123-7.
    • 4 Mazières J, Peters S, Lepage B, Cortot AB, Barlesi F, Beau-Faller M, Besse B, Blons H, Mansuet-Lupo A, Urban T, Moro-Sibilot D, Dansin E, Chouaid C, Wislez M, Diebold J, Felip E, Rouquette I, Milia JD, Gautschi O. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol 2013; 31:1997-2003.
    • 4 de Martino M, Zhuang D, Klatte T, Rieken M, Rouprêt M, Xylinas E, Clozel T, Krzywinski M, Elemento O, Shariat SF. Impact of ERBB2 mutations on in vitro sensitivity of bladder cancer to lapatinib. Cancer Biol Ther 2014; 15:1239-47.
    • EGFR
    • 4 Cappuzzo F, Finocchiaro G, Grossi F, Bidoli P, Favaretto A, Marchetti A, Valente ML, Cseh A, Clementi L, Massey D, Santoro A. Phase II study of afatinib, an irreversible ErbB family blocker, in EGFR FISH-positive non-small-cell lung cancer. J Thorac Oncol 2015; 10:665-72.
    • ERBB2
    • 4 De Grève J, Moran T, Graas MP, Galdermans D, Vuylsteke P, Canon JL, Schallier D, Decoster L, Teugels E, Massey D, Chand VK, Vansteenkiste J. Phase II study of afatinib, an irreversible ErbB family blocker, in demographically and genotypically defined lung adenocarcinoma. Lung Cancer 2015; 88:63-9.
    • EGFR
    • 4 Kobayashi Y, Togashi Y, Yatabe Y, Mizuuchi H, Jangchul P, Kondo C, Shimoji M, Sato K, Suda K, Tomizawa K, Takemoto T, Hida T, Nishio K, Mitsudomi T. EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIs. Clin Cancer Res 2015; 21:5305-13.
    • 4 Gallant JN, Sheehan JH, Shaver TM, Bailey M, Lipson D, Chandramohan R, Red Brewer M, York SJ, Kris MG, Pietenpol JA, Ladanyi M, Miller VA, Ali SM, Meiler J, Lovly CM. EGFR Kinase Domain Duplication (EGFR-KDD) Is a Novel Oncogenic Driver in Lung Cancer That Is Clinically Responsive to Afatinib. Cancer Discov 2015; 5:1155-63.
    • ERBB3
    • 4 Choudhury NJ, Campanile A, Antic T, Yap KL, Fitzpatrick CA, Wade JL 3rd, Karrison T, Stadler WM, Nakamura Y, O'Donnell PH. Afatinib Activity in Platinum-Refractory Metastatic Urothelial Carcinoma in Patients With ERBB Alterations. J Clin Oncol 2016; 34:2165-71.
    • EGFR
    • 4 Kuiper JL, Hashemi SM, Thunnissen E, Snijders PJ, Grünberg K, Bloemena E, Sie D, Postmus PE, Heideman DA, Smit EF. Non-classic EGFR mutations in a cohort of Dutch EGFR-mutated NSCLC patients and outcomes following EGFR-TKI treatment. Br J Cancer 2016; 115:1504-1512.
    • 4 Chiba M, Togashi Y, Bannno E, Kobayashi Y, Nakamura Y, Hayashi H, Terashima M, De Velasco MA, Sakai K, Fujita Y, Mitsudomi T, Nishio K. Efficacy of irreversible EGFR-TKIs for the uncommon secondary resistant EGFR mutations L747S, D761Y, and T854A. BMC Cancer 2017; 17:281.
    • NRG1
    • 4 Gay ND, Wang Y, Beadling C, Warrick A, Neff T, Corless CL, Tolba K. Durable Response to Afatinib in Lung Adenocarcinoma Harboring NRG1 Gene Fusions. J Thorac Oncol 2017; 12:e107-e110.
    • EGFR
    • 4 Ibrahim U, Saqib A, Atallah JP. EGFR exon 18 delE709_T710insD mutated stage IV lung adenocarcinoma with response to afatinib. Lung Cancer 2017; 108:45-47.
    • NRG1
    • 4 Jones MR, Lim H, Shen Y, Pleasance E, Ch'ng C, Reisle C, Leelakumari S, Zhao C, Yip S, Ho J, Zhong E, Ng T, Ionescu D, Schaeffer DF, Mungall AJ, Mungall KL, Zhao Y, Moore RA, Ma Y, Chia S, Ho C, Renouf DJ, Gelmon K, Jones SJM, Marra MA, Laskin J. Successful targeting of the NRG1 pathway indicates novel treatment strategy for metastatic cancer. Ann Oncol 2017; 28:3092-3097.
    • ERBB2
    • 4 Yamamoto H, Toyooka S, Ninomiya T, Matsumoto S, Kanai M, Tomida S, Kiura K, Muto M, Suzawa K, Desmeules P, Kris MG, Li BT, Ladanyi M. Therapeutic Potential of Afatinib for Cancers with ERBB2 (HER2) Transmembrane Domain Mutations G660D and V659E. Oncologist 2018; 23:150-154.
    • EGFR
    • 4 Liu Y, Li Y, Ou Q, Wu X, Wang X, Shao YW, Ying J. Acquired EGFR L718V mutation mediates resistance to osimertinib in non-small cell lung cancer but retains sensitivity to afatinib. Lung Cancer 2018; 118:1-5.
    • ERBB2
    • 4 Goss GD, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Li W, Guclu S, Isla D, Min YJ, Morabito A, Ardizzoni A, Gadgeel SM, Fülöp A, Bühnemann C, Gibson N, Krämer N, Solca F, Cseh A, Ehrnrooth E, Soria JC. Association of ERBB Mutations With Clinical Outcomes of Afatinib- or Erlotinib-Treated Patients With Lung Squamous Cell Carcinoma: Secondary Analysis of the LUX-Lung 8 Randomized Clinical Trial. JAMA Oncol 2018; 4:1189-1197.
    • 4 Nagano M, Kohsaka S, Ueno T, Kojima S, Saka K, Iwase H, Kawazu M, Mano H. High-Throughput Functional Evaluation of Variants of Unknown Significance in ERBB2. Clin Cancer Res 2018; 24:5112-5122.
    • EGFR
    • 4 Wang J, Li X, Xue X, Ou Q, Wu X, Liang Y, Wang X, You M, Shao YW, Zhang Z, Zhang S. Clinical outcomes of EGFR kinase domain duplication to targeted therapies in NSCLC. Int J Cancer 2019; 144:2677-2682.
    • ERBB2
    • 4 Pahuja KB, Nguyen TT, Jaiswal BS, Prabhash K, Thaker TM, Senger K, Chaudhuri S, Kljavin NM, Antony A, Phalke S, Kumar P, Mravic M, Stawiski EW, Vargas D, Durinck S, Gupta R, Khanna-Gupta A, Trabucco SE, Sokol ES, Hartmaier RJ, Singh A, Chougule A, Trivedi V, Dutt A, Patil V, Joshi A, Noronha V, Ziai J, Banavali SD, Ramprasad V, DeGrado WF, Bueno R, Jura N, Seshagiri S. Actionable Activating Oncogenic ERBB2/HER2 Transmembrane and Juxtamembrane Domain Mutations. Cancer Cell 2018; 34:792-806.e5.
    • NRG1
    • 4 Jones MR, Williamson LM, Topham JT, Lee MKC, Goytain A, Ho J, Denroche RE, Jang G, Pleasance E, Shen Y, Karasinska JM, McGhie JP, Gill S, Lim HJ, Moore MJ, Wong HL, Ng T, Yip S, Zhang W, Sadeghi S, Reisle C, Mungall AJ, Mungall KL, Moore RA, Ma Y, Knox JJ, Gallinger S, Laskin J, Marra MA, Schaeffer DF, Jones SJM, Renouf DJ. NRG1 Gene Fusions Are Recurrent, Clinically Actionable Gene Rearrangements in KRAS Wild-Type Pancreatic Ductal Adenocarcinoma. Clin Cancer Res 2019; 25:4674-4681.
    • EGFR
    • 4 Truini A, Starrett JH, Stewart T, Ashtekar K, Walther Z, Wurtz A, Lu D, Park JH, DeVeaux M, Song X, Gettinger S, Zelterman D, Lemmon MA, Goldberg SB, Politi K. The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma. Clin Cancer Res 2019; 25:6382-6391.
    • 4 Liang SK, Ko JC, Yang JC, Shih JY. Afatinib is effective in the treatment of lung adenocarcinoma with uncommon EGFR p.L747P and p.L747S mutations. Lung Cancer 2019; 133:103-109.
    • ERBB2
    • 4 Hsu CC, Liao BC, Liao WY, Markovets A, Stetson D, Thress K, Yang JC. Exon 16-Skipping HER2 as a Novel Mechanism of Osimertinib Resistance in EGFR L858R/T790M-Positive Non-Small Cell Lung Cancer. J Thorac Oncol 2020; 15:50-61.
    • EGFR
    • 4 Wang XF, Zhao QT, Chen C. Afatinib Achieved Remarkable Disease Control in a Chinese Patient With Lung Adenocarcinoma Harboring Rare EGFR Exon 18-25 Kinase Domain Duplication. Am J Ther 2020 Sep/Oct;27:e535-e537.
    • ERBB2
    • 4 Robichaux JP, Elamin YY, Vijayan RSK, Nilsson MB, Hu L, He J, Zhang F, Pisegna M, Poteete A, Sun H, Li S, Chen T, Han H, Negrao MV, Ahnert JR, Diao L, Wang J, Le X, Meric-Bernstam F, Routbort M, Roeck B, Yang Z, Raymond VM, Lanman RB, Frampton GM, Miller VA, Schrock AB, Albacker LA, Wong KK, Cross JB, Heymach JV. Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 Activity. Cancer Cell 2019; 36:444-457.e7.
    • EGFR
    • 4 Chen Q, Huang Y, Shao L, Han-Zhang H, Yang F, Wang Y, Liu J, Gan J. An EGFR-Amplified Cervical Squamous Cell Carcinoma Patient with Pulmonary Metastasis Benefits from Afatinib: A Case Report. Onco Targets Ther 2020; 13:1845-1849. eCollection 2020.
    • ERBB2
    • 4 Gaibar M, Beltrán L, Romero-Lorca A, Fernández-Santander A, Novillo A. Somatic Mutations in HER2 and Implications for Current Treatment Paradigms in HER2-Positive Breast Cancer. J Oncol 2020; 2020:6375956. eCollection 2020.
    • EGFR
    • 4 He SY, Lin QF, Chen J, Yu GP, Zhang JL, Shen D. Efficacy of afatinib in a patient with rare EGFR (G724S/R776H) mutations and amplification in lung adenocarcinoma: A case report. World J Clin Cases 2021; 9:1329-1335.
    • 4 Nishino M, Suda K, Koga T, Ohara S, Fujino T, Soh J, Tirunagaru V, Vellanki A, Doebele RC, Mitsudomi T. Activity of tarloxotinib-E in cells with EGFR exon-20 insertion mutations and mechanisms of acquired resistance. Thorac Cancer 2021; 12:1511-1516.
    • NRG1
    • 4 Drilon A, Duruisseaux M, Han JY, Ito M, Falcon C, Yang SR, Murciano-Goroff YR, Chen H, Okada M, Molina MA, Wislez M, Brun P, Dupont C, Branden E, Rossi G, Schrock A, Ali S, Gounant V, Magne F, Blum TG, Schram AM, Monnet I, Shih JY, Sabari J, Pérol M, Zhu VW, Nagasaka M, Doebele R, Camidge DR, Arcila M, Ignatius Ou SH, Moro-Sibilot D, Rosell R, Muscarella LA, Liu SV, Cadranel J. Clinicopathologic Features and Response to Therapy of NRG1 Fusion-Driven Lung Cancers: The eNRGy1 Global Multicenter Registry. J Clin Oncol 2021 Jun 2:JCO2003307. [Epub ahead of print]
    • EGFR
    • 4 Wei Y, Cui Y, Guo Y, Li L, Zeng L. A Lung Adenocarcinoma Patient With a Rare EGFR E709_T710delinsD Mutation Showed a Good Response to Afatinib Treatment: A Case Report and Literature Review. Front Oncol 2021; 11:700345. eCollection 2021.
    • 4 Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 2021; 597:732-737.
    • 4 Fang YF, Liu PC. Afatinib and osimertinib in lung adenocarcinoma harbored EGFR T751_I759delinsS mutation: A case report. Thorac Cancer 2021 Nov 2. [Epub ahead of print]
    • Afatinib + Bevacizumab
    • EGFR
    • 4 Xu H, Shao C. KIF5B-EGFR Fusion: A Novel EGFR Mutation in Lung Adenocarcinoma. Onco Targets Ther 2020; 13:8317-8321. eCollection 2020.
    • Afatinib + Selumetinib
    • KRAS+ERBB3
    • 4 Sun C, Hobor S, Bertotti A, Zecchin D, Huang S, Galimi F, Cottino F, Prahallad A, Grernrum W, Tzani A, Schlicker A, Wessels LF, Smit EF, Thunnissen E, Halonen P, Lieftink C, Beijersbergen RL, Di Nicolantonio F, Bardelli A, Trusolino L, Bernards R. Intrinsic resistance to MEK inhibition in KRAS mutant lung and colon cancer through transcriptional induction of ERBB3. Cell Rep 2014; 7:86-93.
    • Afatinib + Temozolomide
    • EGFR
    • 4 Alshami J, Guiot MC, Owen S, Kavan P, Gibson N, Solca F, Cseh A, Reardon DA, Muanza T. Afatinib, an irreversible ErbB family blocker, with protracted temozolomide in recurrent glioblastoma: a case report. Oncotarget 2015; 6:34030-7.
    • Agerafenib
    • RET
    • R2 Hida T, Velcheti V, Reckamp KL, Nokihara H, Sachdev P, Kubota T, Nakada T, Dutcus CE, Ren M, Tamura T. A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma. Lung Cancer 2019; 138:124-130.
    • RET
    • 4 Hida T, Velcheti V, Reckamp KL, Nokihara H, Sachdev P, Kubota T, Nakada T, Dutcus CE, Ren M, Tamura T. A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma. Lung Cancer 2019; 138:124-130.
    • Alectinib
    • ALK
    • R2 J. Jean Cui, Evan Rogers, Dayong Zhai, Wei Deng, Jane Ung, Vivian Nguyen, Han Zhang, Xin Zhang, Ana Parra, Maria Barrera, Dong Lee, Brion Murray. TPX-0131: A next generation macrocyclic ALK inhibitor that overcomes ALK resistant mutations refractory to current approved ALK inhibitors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5226.
    • R2 Katayama R, Friboulet L, Koike S, Lockerman EL, Khan TM, Gainor JF, Iafrate AJ, Takeuchi K, Taiji M, Okuno Y, Fujita N, Engelman JA, Shaw AT. Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib. Clin Cancer Res 2014; 20:5686-96.
    • R2 Hatcher JM, Bahcall M, Choi HG, Gao Y, Sim T, George R, Jänne PA, Gray NS. Discovery of Inhibitors That Overcome the G1202R Anaplastic Lymphoma Kinase Resistance Mutation. J Med Chem 2015; 58:9296-9308.
    • R2 Holla VR, Elamin YY, Bailey AM, Johnson AM, Litzenburger BC, Khotskaya YB, Sanchez NS, Zeng J, Shufean MA, Shaw KR, Mendelsohn J, Mills GB, Meric-Bernstam F, Simon GR. ALK: a tyrosine kinase target for cancer therapy. Cold Spring Harb Mol Case Stud 2017; 3:a001115.
    • R2 Lin JJ, Riely GJ, Shaw AT. Targeting ALK: Precision Medicine Takes on Drug Resistance. Cancer Discov 2017; 7:137-155.
    • R2 Lin JJ, Zhu VW, Schoenfeld AJ, Yeap BY, Saxena A, Ferris LA, Dagogo-Jack I, Farago AF, Taber A, Traynor A, Menon S, Gainor JF, Lennerz JK, Plodkowski AJ, Digumarthy SR, Ou SI, Shaw AT, Riely GJ. Brigatinib in Patients With Alectinib-Refractory ALK-Positive NSCLC. J Thorac Oncol 2018; 13:1530-1538.
    • ALK
    • 1 Hida T, Nokihara H, Kondo M, Kim YH, Azuma K, Seto T, Takiguchi Y, Nishio M, Yoshioka H, Imamura F, Hotta K, Watanabe S, Goto K, Satouchi M, Kozuki T, Shukuya T, Nakagawa K, Mitsudomi T, Yamamoto N, Asakawa T, Asabe R, Tanaka T, Tamura T. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet 2017; 390:29-39.
    • 1 Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, Ou SI, Pérol M, Dziadziuszko R, Rosell R, Zeaiter A, Mitry E, Golding S, Balas B, Noe J, Morcos PN, Mok T; ALEX Trial Investigators. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med 2017; 377:829-838.
    • ALK
    • 3 Lin JJ, Riely GJ, Shaw AT. Targeting ALK: Precision Medicine Takes on Drug Resistance. Cancer Discov 2017; 7:137-155.
    • ALK
    • 4 Hu C, Zhao L, Wu F. Different response to ALK inhibitors in EML4-ALK positive mediastinal cancer of unknown primary. J Clin Oncol 2020; 38(15_suppl): 104-104.
    • 4 Kelly AD, Wiklund T, Kononen J, Creeden J, Section: . STRN-ALK Fusion-Positive Case of Breast Cancer With Response to Alectinib. JCO Prec Oncol 2021; 10.1200/PO.21.00142 5 1281-1284. Published online August 11, 2021.
    • 4 Saiki M, Ohyanagi F, Ariyasu R, Koyama J, Sonoda T, Nishikawa S, Kitazono S, Yanagitani N, Horiike A, Ninomiya H, Ishikawa Y, Nishio M. Dramatic response to alectinib in inflammatory myofibroblastic tumor with anaplastic lymphoma kinase fusion gene. Jpn J Clin Oncol 2017; 47:1189-1192.
    • 4 Ross JS, Ali SM, Fasan O, Block J, Pal S, Elvin JA, Schrock AB, Suh J, Nozad S, Kim S, Jeong Lee H, Sheehan CE, Jones DM, Vergilio JA, Ramkissoon S, Severson E, Daniel S, Fabrizio D, Frampton G, Miller VA, Stephens PJ, Gay LM. ALK Fusions in a Wide Variety of Tumor Types Respond to Anti-ALK Targeted Therapy. Oncologist 2017; 22:1444-1450.
    • 4 Heath JA, Campbell MA, Thomas A, Solomon B. Good clinical response to alectinib, a second generation ALK inhibitor, in refractory neuroblastoma. Pediatr Blood Cancer 2018; 65:e27055.
    • 4 Zhu VW, Schrock AB, Bosemani T, Benn BS, Ali SM, Ou SI. Dramatic response to alectinib in a lung cancer patient with a novel VKORC1L1-ALK fusion and an acquired ALK T1151K mutation. Lung Cancer (Auckl) 2018; 9:111-116. eCollection 2018.
    • 4 Honda K, Kadowaki S, Kato K, Hanai N, Hasegawa Y, Yatabe Y, Muro K. Durable response to the ALK inhibitor alectinib in inflammatory myofibroblastic tumor of the head and neck with a novel SQSTM1-ALK fusion: a case report. Invest New Drugs 2019; 37:791-795.
    • 4 Li Y, Chen X, Qu Y, Fan JM, Li Y, Peng H, Zheng Y, Zhang Y, Zhang HB. Partial Response to Ceritinib in a Patient With Abdominal Inflammatory Myofibroblastic Tumor Carrying a TFG-ROS1 Fusion. J Natl Compr Canc Netw 2019; 17:1459-1462.
    • Alkylating agent
    • MGMT
    • 4 Halford S, Rowan A, Sawyer E, Talbot I, Tomlinson I. O(6)-methylguanine methyltransferase in colorectal cancers: detection of mutations, loss of expression, and weak association with G:C>A:T transitions. Gut 2005; 54:797-802.
    • Alpelisib
    • PIK3CA
    • 4 Juric D, Rodon J, Tabernero J, Janku F, Burris HA, Schellens JHM, Middleton MR, Berlin J, Schuler M, Gil-Martin M, Rugo HS, Seggewiss-Bernhardt R, Huang A, Bootle D, Demanse D, Blumenstein L, Coughlin C, Quadt C, Baselga J. Phosphatidylinositol 3-Kinase α-Selective Inhibition With Alpelisib (BYL719) in PIK3CA-Altered Solid Tumors: Results From the First-in-Human Study. J Clin Oncol 2018; 36:1291-1299.
    • 4 Vasan N, Razavi P, Johnson JL, Shao H, Shah H, Antoine A, Ladewig E, Gorelick A, Lin TY, Toska E, Xu G, Kazmi A, Chang MT, Taylor BS, Dickler MN, Jhaveri K, Chandarlapaty S, Rabadan R, Reznik E, Smith ML, Sebra R, Schimmoller F, Wilson TR, Friedman LS, Cantley LC, Scaltriti M, Baselga J. Double PIK3CA mutations in cis increase oncogenicity and sensitivity to PI3Kα inhibitors. Science 2019; 366:714-723.
    • Alpelisib + Fulvestrant
    • PIK3CA
    • 3 Rugo HS, Lerebours F, Ciruelos E, Drullinsky P, Ruiz-Borrego M, Neven P, Park YH, Prat A, Bachelot T, Juric D, Turner N, Sophos N, Zarate JP, Arce C, Shen YM, Turner S, Kanakamedala H, Hsu WC, Chia S. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study. Lancet Oncol 2021; 22:489-498.
    • Alrizomadlin + Pembrolizumab
    • ATM+TP53, STK11
    • 4 Tolcher AW, Reeves JA, McKean M, Chmielowski B, Beck JT, Shaheen MF, Somaiah N, Wilson M, Spira AI, Drabick JJ, Tang Y, Winkler R, Li M, Ahmad M, Lu M, Liang Z, Yang D, Zhai Y. Preliminary results of a phase II study of alrizomadlin (APG-115), a novel, small-molecule MDM2 inhibitor, in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (I-O) drugs. J Clin Oncol 2021; 39(15_suppl): 2506-2506.
    • Amatuximab
    • MSLN
    • 4 Hassan R, Kindler HL, Jahan T, Bazhenova L, Reck M, Thomas A, Pastan I, Parno J, O'Shannessy DJ, Fatato P, Maltzman JD, Wallin BA. Phase II clinical trial of amatuximab, a chimeric antimesothelin antibody with pemetrexed and cisplatin in advanced unresectable pleural mesothelioma. Clin Cancer Res 2014; 20:5927-36.
    • Amivantamab
    • EGFR
    • 2 Haura EB, Cho BC, Lee JS, Han J, Lee KH, Sanborn RE, Govindan R, Cho EK, Kim S, Reckamp KL, Sabari JK, Thayu M, Bae K, Knoblauch RE, Curtin J, Haddish-Berhane N, Sherman LJ, Lorenzi MV, Park K, Bauml J, PA P. JNJ-61186372 (JNJ-372), an EGFR-cMet bispecific antibody, in EGFR-driven advanced non-small cell lung cancer (NSCLC). J Clin Oncol 2019; 37(15_suppl): 9009-9009.
    • 2 Park K, John T, Kim S, Lee JS, Shu CA, Kim D, Ramirez SV, Spira AI, Sabari JK, Han J, Trigo JM, Lee CK, Lee KH, Girard N, Lorenzini PA, Xie J, Roshak A, Thayu M, Knoblauch RE, Cho BC. Amivantamab (JNJ-61186372), an anti-EGFR-MET bispecific antibody, in patients with EGFR exon 20 insertion (exon20ins)-mutated non-small cell lung cancer (NSCLC). J Clin Oncol 2020; 38(15_suppl): 9512-9512.
    • 2 Yun J, Lee SH, Kim SY, Jeong SY, Kim JH, Pyo KH, Park CW, Heo SG, Yun MR, Lim S, Lim SM, Hong MH, Kim HR, Thayu M, Curtin JC, Knoblauch RE, Lorenzi MV, Roshak A, Cho BC. Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC. Cancer Discov 2020; 10:1194-1209.
    • 2 Park K, Haura EB, Leighl NB, Mitchell P, Shu CA, Girard N, Viteri S, Han JY, Kim SW, Lee CK, Sabari JK, Spira AI, Yang TY, Kim DW, Lee KH, Sanborn RE, Trigo J, Goto K, Lee JS, Yang JC, Govindan R, Bauml JM, Garrido P, Krebs MG, Reckamp KL, Xie J, Curtin JC, Haddish-Berhane N, Roshak A, Millington D, Lorenzini P, Thayu M, Knoblauch RE, Cho BC. Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study. J Clin Oncol 2021; 39:3391-3402.
    • MET
    • 4 Spira A, Krebs M, Cho B, Besse B, Goldman J, Janne P, Lee C, Ma Z, Mansfield A, Minchom A, Ou S, Salgia R, Wang Z, Gao G, Curtin J, Roshak A, Schnepp R, Thayu M, Knoblauch R, Trigo J. OA15.03 Amivantamab in Non-small Cell Lung Cancer (NSCLC) with MET Exon 14 Skipping (METex14) Mutation: Initial Results from CHRYSALIS. J Thorac Oncol 2021; 16 (10): S874. 10.1016/j.jtho.2021.08.084
    • EGFR+MET
    • 4 Haura EB, Cho BC, Lee JS, Han J, Lee KH, Sanborn RE, Govindan R, Cho EK, Kim S, Reckamp KL, Sabari JK, Thayu M, Bae K, Knoblauch RE, Curtin J, Haddish-Berhane N, Sherman LJ, Lorenzi MV, Park K, Bauml J, PA P. JNJ-61186372 (JNJ-372), an EGFR-cMet bispecific antibody, in EGFR-driven advanced non-small cell lung cancer (NSCLC). J Clin Oncol 2019; 37(15_suppl): 9009-9009.
    • Amivantamab + Lazertinib
    • MET
    • R2 Bauml J, Cho BC, Park K, Lee KH, CHO EK, Kim D, Kim S, Haura EB, Sabari JK, Sanborn RE, Nagasaka M, Ou SI, Minchom AR, Gomez JE, Curtin JC, Gao G, Roshak A, Thayu M, Knoblauch RE, Spira AI, Sinai , York N, R&D NJ, House S, Specialists PUORC, Fairfax , VA . Amivantamab in combination with lazertinib for the treatment of osimertinib-relapsed, chemotherapy-naïve EGFR mutant (EGFRm) non-small cell lung cancer (NSCLC) and potential biomarkers for response. J Clin Oncol 2021; 39(15_suppl): 9006-9006.
    • EGFR
    • 3 Cho B, Lee K, Cho E, Kim D, Lee J, Han J, Kim S, Spira A, Haura E, Sabari J, Sanborn R, Bauml J, Gomez J, Lorenzini P, Infante J, Xie J, Haddish-Berhane N, Thayu M, Knoblauch R, Park K. 1258O Amivantamab (JNJ-61186372), an EGFR-MET bispecific antibody, in combination with lazertinib, a 3rd-generation tyrosine kinase inhibitor (TKI), in advanced EGFR NSCLC. Ann Oncol 2020; 31 (4): S813. 10.1016/j.annonc.2020.08.1572
    • EGFR, EGFR+EGFR, EGFR+MET, MET
    • 3 Bauml J, Cho BC, Park K, Lee KH, CHO EK, Kim D, Kim S, Haura EB, Sabari JK, Sanborn RE, Nagasaka M, Ou SI, Minchom AR, Gomez JE, Curtin JC, Gao G, Roshak A, Thayu M, Knoblauch RE, Spira AI, Sinai , York N, R&D NJ, House S, Specialists PUORC, Fairfax , VA . Amivantamab in combination with lazertinib for the treatment of osimertinib-relapsed, chemotherapy-naïve EGFR mutant (EGFRm) non-small cell lung cancer (NSCLC) and potential biomarkers for response. J Clin Oncol 2021; 39(15_suppl): 9006-9006.
    • Anastrozole
    • ESR1
    • R2 Jeselsohn R, Buchwalter G, De Angelis C, Brown M, Schiff R. ESR1 mutations—a mechanism for acquired endocrine resistance in breast cancer. Nat Rev Clin Oncol 2015; 12:573-83.
    • PGR
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    • 1 Stuart NS, Warwick J, Blackledge GR, Spooner D, Keen C, Taylor AR, Tyrell C, Webster DJ, Earl H. A randomised phase III cross-over study of tamoxifen versus megestrol acetate in advanced and recurrent breast cancer. Eur J Cancer 1996; 32A:1888-92.
    • 1 Taylor CW, Green S, Dalton WS, Martino S, Rector D, Ingle JN, Robert NJ, Budd GT, Paradelo JC, Natale RB, Bearden JD, Mailliard JA, Osborne CK. Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer: an intergroup study. J Clin Oncol 1998; 16:994-9.
    • 1 The Exemestane Study Group. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial.. J Clin Oncol 2000; 18:1399-411.
    • 1 Mouridsen H, Gershanovich M, Sun Y, Pérez-Carrión R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Jänicke F, Pluzanska A, Dank M, Becquart D, Bapsy PP, Salminen E, Snyder R, Lassus M, Verbeek JA, Staffler B, Chaudri-Ross HA, Dugan M. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 2001; 19:2596-606.
    • ESR1, PGR
    • 1 Bonneterre J, Buzdar A, Nabholtz JM, Robertson JF, Thürlimann B, von Euler M, Sahmoud T, Webster A, Steinberg M; Arimidex Writing Committee; Investigators Committee Members. Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma. Cancer 2001; 92:2247-58.
    • ESR1
    • 4 van Weelden WJ, Massuger LFAG; ENITEC, Pijnenborg JMA, Romano A. Anti-estrogen Treatment in Endometrial Cancer: A Systematic Review. Front Oncol 2019; 9:359. eCollection 2019.
    • Androgen receptor antagonist
    • AR, AURKA, MYCN, RB1, TP53
    • R2 Watson PA, Arora VK, Sawyers CL. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nat Rev Cancer 2015; 15:701-11.
    • AR
    • 4 Munoz J, Wheler JJ, Kurzrock R. Androgen receptors beyond prostate cancer: an old marker as a new target. Oncotarget 2015; 6:592-603.
    • Anetumab Ravtansine
    • MSLN
    • 4 Hassan R, Blumenschein GR Jr, Moore KN, Santin AD, Kindler HL, Nemunaitis JJ, Seward SM, Thomas A, Kim SK, Rajagopalan P, Walter AO, Laurent D, Childs BH, Sarapa N, Elbi C, Bendell JC. First-in-Human, Multicenter, Phase I Dose-Escalation and Expansion Study of Anti-Mesothelin Antibody-Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors. J Clin Oncol 2020; 38:1824-1835.
    • Anlotinib
    • FGFR3
    • 4 Wang Y, Liang D, Chen J, Chen H, Fan R, Gao Y, Gao Y, Tao R, Zhang H. Targeted Therapy with Anlotinib for a Patient with an Oncogenic FGFR3-TACC3 Fusion and Recurrent Glioblastoma. Oncologist 2021; 26:173-177.
    • Anti-CTLA-4 monoclonal antibody
    • CDKN2A
    • R2 Adib E, Nassar AH, Akl EW, Abou Alaiwi S, Nuzzo PV, Mouhieddine TH, Sonpavde G, Haddad RI, Mouw KW, Giannakis M, Hodi FS, Shukla SA, Gusev A, Braun DA, Choueiri TK, Kwiatkowski DJ. CDKN2A Alterations and Response to Immunotherapy in Solid Tumors. Clin Cancer Res 2021; 27:4025-4035.
    • HLA-A
    • R2 Naranbhai V, Viard M, Dean M, Groha S, Braun DA, Labaki C, Shukla SA, Yuki Y, Shah P, Chin K, Wind-Rotolo M, Mu XJ, Robbins PB, Gusev A, Choueiri TK, Gulley JL, Carrington M. HLA-A*03 and response to immune checkpoint blockade in cancer: an epidemiological biomarker study. Lancet Oncol 2022; 23:172-184.
    • EPHA7
    • 4 Zhang Z, Wu HX, Lin WH, Wang ZX, Yang LP, Zeng ZL, Luo HY. EPHA7 mutation as a predictive biomarker for immune checkpoint inhibitors in multiple cancers. BMC Med 2021; 19:26.
    • Anti-ERBB3 monoclonal antibody
    • ERBB3
    • 4 Hyman DM, Piha-Paul SA, Won H, Rodon J, Saura C, Shapiro GI, Juric D, Quinn DI, Moreno V, Doger B, Mayer IA, Boni V, Calvo E, Loi S, Lockhart AC, Erinjeri JP, Scaltriti M, Ulaner GA, Patel J, Tang J, Beer H, Selcuklu SD, Hanrahan AJ, Bouvier N, Melcer M, Murali R, Schram AM, Smyth LM, Jhaveri K, Li BT, Drilon A, Harding JJ, Iyer G, Taylor BS, Berger MF, Cutler RE Jr, Xu F, Butturini A, Eli LD, Mann G, Farrell C, Lalani AS, Bryce RP, Arteaga CL, Meric-Bernstam F, Baselga J, Solit DB. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature 2018; 554:189-194.
    • Anti-PD-1 monoclonal antibody
    • EGFR
    • R2 Lee CK, Man J, Lord S, Cooper W, Links M, Gebski V, Herbst RS, Gralla RJ, Mok T, Yang JC. Clinical and Molecular Characteristics Associated With Survival Among Patients Treated With Checkpoint Inhibitors for Advanced Non-Small Cell Lung Carcinoma: A Systematic Review and Meta-analysis. JAMA Oncol 2018; 4:210-216.
    • STK11, STK11+KRAS
    • R2 Skoulidis F, Goldberg ME, Greenawalt DM, Hellmann MD, Awad MM, Gainor JF, Schrock AB, Hartmaier RJ, Trabucco SE, Gay L, Ali SM, Elvin JA, Singal G, Ross JS, Fabrizio D, Szabo PM, Chang H, Sasson A, Srinivasan S, Kirov S, Szustakowski J, Vitazka P, Edwards R, Bufill JA, Sharma N, Ou SI, Peled N, Spigel DR, Rizvi H, Aguilar EJ, Carter BW, Erasmus J, Halpenny DF, Plodkowski AJ, Long NM, Nishino M, Denning WL, Galan-Cobo A, Hamdi H, Hirz T, Tong P, Wang J, Rodriguez-Canales J, Villalobos PA, Parra ER, Kalhor N, Sholl LM, Sauter JL, Jungbluth AA, Mino-Kenudson M, Azimi R, Elamin YY, Zhang J, Leonardi GC, Jiang F, Wong KK, Lee JJ, Papadimitrakopoulou VA, Wistuba II, Miller VA, Frampton GM, Wolchok JD, Shaw AT, Jänne PA, Stephens PJ, Rudin CM, Geese WJ, Albacker LA, Heymach JV. STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS-Mutant Lung Adenocarcinoma. Cancer Discov 2018; 8:822-835.
    • ALK
    • R2 Mazieres J, Drilon A, Lusque A, Mhanna L, Cortot AB, Mezquita L, Thai AA, Mascaux C, Couraud S, Veillon R, Van den Heuvel M, Neal J, Peled N, Früh M, Ng TL, Gounant V, Popat S, Diebold J, Sabari J, Zhu VW, Rothschild SI, Bironzo P, Martinez-Marti A, Curioni-Fontecedro A, Rosell R, Lattuca-Truc M, Wiesweg M, Besse B, Solomon B, Barlesi F, Schouten RD, Wakelee H, Camidge DR, Zalcman G, Novello S, Ou SI, Milia J, Gautschi O. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol 2019; 30:1321-1328.
    • Mismatch repair, Tumour Mutational Burden
    • R2 Touat M, Li YY, Boynton AN, Spurr LF, Iorgulescu JB, Bohrson CL, Cortes-Ciriano I, Birzu C, Geduldig JE, Pelton K, Lim-Fat MJ, Pal S, Ferrer-Luna R, Ramkissoon SH, Dubois F, Bellamy C, Currimjee N, Bonardi J, Qian K, Ho P, Malinowski S, Taquet L, Jones RE, Shetty A, Chow KH, Sharaf R, Pavlick D, Albacker LA, Younan N, Baldini C, Verreault M, Giry M, Guillerm E, Ammari S, Beuvon F, Mokhtari K, Alentorn A, Dehais C, Houillier C, Laigle-Donadey F, Psimaras D, Lee EQ, Nayak L, McFaline-Figueroa JR, Carpentier A, Cornu P, Capelle L, Mathon B, Barnholtz-Sloan JS, Chakravarti A, Bi WL, Chiocca EA, Fehnel KP, Alexandrescu S, Chi SN, Haas-Kogan D, Batchelor TT, Frampton GM, Alexander BM, Huang RY, Ligon AH, Coulet F, Delattre JY, Hoang-Xuan K, Meredith DM, Santagata S, Duval A, Sanson M, Cherniack AD, Wen PY, Reardon DA, Marabelle A, Park PJ, Idbaih A, Beroukhim R, Bandopadhayay P, Bielle F, Ligon KL. Mechanisms and therapeutic implications of hypermutation in gliomas. Nature 2020; 580:517-523.
    • CDKN2A
    • R2 Adib E, Nassar AH, Akl EW, Abou Alaiwi S, Nuzzo PV, Mouhieddine TH, Sonpavde G, Haddad RI, Mouw KW, Giannakis M, Hodi FS, Shukla SA, Gusev A, Braun DA, Choueiri TK, Kwiatkowski DJ. CDKN2A Alterations and Response to Immunotherapy in Solid Tumors. Clin Cancer Res 2021; 27:4025-4035.
    • HLA-A
    • R2 Naranbhai V, Viard M, Dean M, Groha S, Braun DA, Labaki C, Shukla SA, Yuki Y, Shah P, Chin K, Wind-Rotolo M, Mu XJ, Robbins PB, Gusev A, Choueiri TK, Gulley JL, Carrington M. HLA-A*03 and response to immune checkpoint blockade in cancer: an epidemiological biomarker study. Lancet Oncol 2022; 23:172-184.
    • LRP1B
    • 4 Brown LC, Sedhom R, Schwartz EB, Zhu J, Kao C, Tucker MD, Labriola M, Gupta RT, Marin D, Wu Y, Zhang T, Harrison MR, George DJ, Alva AS, Antonarakis ES, Armstrong AJ. Association of LRP1B pathogenic genomic alterations with favorable outcomes with immune checkpoint inhibitors across multiple tumor types. J Clin Oncol 2020; 38(15_suppl): 3007-3007.
    • POLE
    • 4 Garmezy B, Gheeya JS, Thein KZ, Pilie PG, Wang W, Ahnert JR, Shaw KR, Meric-Bernstam F, Yap TA. Correlation of pathogenic POLE mutations with clinical benefit to immune checkpoint inhibitor therapy. J Clin Oncol 2020; 38(15_suppl): 3008-3008.
    • CD274, PDCD1LG2
    • 4 Sorscher S, Goodman M, Ramkissoon S. Acquired Resistance to Immune Checkpoint Inhibitor Therapy Through Outgrowth of Cells Lacking CD274 and PDCD1LG2 Amplification. JCO Prec Oncol 2018; - published online May 9, 2018
    • MLH1, MSH2, MSH6, PMS2
    • 4 Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A 1999; 96:8681-6.
    • 4 Rosty C, Clendenning M, Walsh MD, Eriksen SV, Southey MC, Winship IM, Macrae FA, Boussioutas A, Poplawski NK, Parry S, Arnold J, Young JP, Casey G, Haile RW, Gallinger S, Le Marchand L, Newcomb PA, Potter JD, DeRycke M, Lindor NM, Thibodeau SN, Baron JA, Win AK, Hopper JL, Jenkins MA, Buchanan DD; Colon Cancer Family Registry Cohort. Germline mutations in PMS2 and MLH1 in individuals with solitary loss of PMS2 expression in colorectal carcinomas from the Colon Cancer Family Registry Cohort. BMJ Open 2016; 6:e010293.
    • POLE
    • 4 Santin AD, Bellone S, Buza N, Choi J, Schwartz PE, Schlessinger J, Lifton RP. Regression of Chemotherapy-Resistant Polymerase ε (POLE) Ultra-Mutated and MSH6 Hyper-Mutated Endometrial Tumors with Nivolumab. Clin Cancer Res 2016; 22:5682-5687.
    • CD274
    • 4 Gröschel S, Bommer M, Hutter B, Budczies J, Bonekamp D, Heining C, Horak P, Fröhlich M, Uhrig S, Hübschmann D, Geörg C, Richter D, Pfarr N, Pfütze K, Wolf S, Schirmacher P, Jäger D, von Kalle C, Brors B, Glimm H, Weichert W, Stenzinger A, Fröhling S. Integration of genomics and histology revises diagnosis and enables effective therapy of refractory cancer of unknown primary with PDL1 amplification. Cold Spring Harb Mol Case Stud 2016; 2:a001180.
    • 4 Ikeda S, Goodman AM, Cohen PR, Jensen TJ, Ellison CK, Frampton G, Miller V, Patel SP, Kurzrock R. Metastatic basal cell carcinoma with amplification of PD-L1: exceptional response to anti-PD1 therapy. NPJ Genom Med 2016;1. pii: 16037.
    • ARID1A
    • 4 Shen J, Ju Z, Zhao W, Wang L, Peng Y, Ge Z, Nagel ZD, Zou J, Wang C, Kapoor P, Ma X, Ma D, Liang J, Song S, Liu J, Samson LD, Ajani JA, Li GM, Liang H, Shen X, Mills GB, Peng G. ARID1A deficiency promotes mutability and potentiates therapeutic antitumor immunity unleashed by immune checkpoint blockade. Nat Med 2018; 24:556-562.
    • CD274
    • 4 Goodman AM, Piccioni D, Kato S, Boichard A, Wang HY, Frampton G, Lippman SM, Connelly C, Fabrizio D, Miller V, Sicklick JK, Kurzrock R. Prevalence of PDL1 Amplification and Preliminary Response to Immune Checkpoint Blockade in Solid Tumors. JAMA Oncol 2018; 4:1237-1244.
    • CDK12
    • 4 Wu YM, Cieślik M, Lonigro RJ, Vats P, Reimers MA, Cao X, Ning Y, Wang L, Kunju LP, de Sarkar N, Heath EI, Chou J, Feng FY, Nelson PS, de Bono JS, Zou W, Montgomery B, Alva A; PCF/SU2C International Prostate Cancer Dream Team, Robinson DR, Chinnaiyan AM. Inactivation of CDK12 Delineates a Distinct Immunogenic Class of Advanced Prostate Cancer. Cell 2018; 173:1770-1782.e14.
    • Tumour Mutational Burden
    • 4 Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, Barron DA, Zehir A, Jordan EJ, Omuro A, Kaley TJ, Kendall SM, Motzer RJ, Hakimi AA, Voss MH, Russo P, Rosenberg J, Iyer G, Bochner BH, Bajorin DF, Al-Ahmadie HA, Chaft JE, Rudin CM, Riely GJ, Baxi S, Ho AL, Wong RJ, Pfister DG, Wolchok JD, Barker CA, Gutin PH, Brennan CW, Tabar V, Mellinghoff IK, DeAngelis LM, Ariyan CE, Lee N, Tap WD, Gounder MM, D'Angelo SP, Saltz L, Stadler ZK, Scher HI, Baselga J, Razavi P, Klebanoff CA, Yaeger R, Segal NH, Ku GY, DeMatteo RP, Ladanyi M, Rizvi NA, Berger MF, Riaz N, Solit DB, Chan TA, Morris LGT. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet 2019; 51:202-206.
    • 4 Goodman AM, Sokol ES, Frampton GM, Lippman SM, Kurzrock R. Microsatellite-Stable Tumors with High Mutational Burden Benefit from Immunotherapy. Cancer Immunol Res 2019; 7:1570-1573.
    • POLE
    • 4 Wang F, Zhao Q, Wang YN, Jin Y, He MM, Liu ZX, Xu RH. Evaluation of POLE and POLD1 Mutations as Biomarkers for Immunotherapy Outcomes Across Multiple Cancer Types. JAMA Oncol 2019 Aug 15. [Epub ahead of print]
    • PRKDC
    • 4 Tan KT, Yeh CN, Chang YC, Cheng JH, Fang WL, Yeh YC, Wang YC, Hsu DS, Wu CE, Lai JI, Chang PM, Chen MH, Lu ML, Chen SJ, Chao Y, Hsiao M, Chen MH. PRKDC: new biomarker and drug target for checkpoint blockade immunotherapy. J Immunother Cancer 2020; 8(1). pii: e000485.
    • 4 Chen Y, Li Y, Guan Y, Huang Y, Lin J, Chen L, Li J, Chen G, Pan LK, Xia X, Xu N, Chang L, Guo Z, Pan J, Yi X, Chen C. Prevalence of PRKDC mutations and association with response to immune checkpoint inhibitors in solid tumors. Mol Oncol 2020; 14:2096-2110.
    • ARID2
    • 4 Fukumoto T, Lin J, Fatkhutdinov N, Liu P, Somasundaram R, Herlyn M, Zhang R, Nishigori C. ARID2 Deficiency Correlates with the Response to Immune Checkpoint Blockade in Melanoma. J Invest Dermatol 2020 Dec 15. pii: S0022-202X(20)32396-4. [Epub ahead of print]
    • EPHA7
    • 4 Zhang Z, Wu HX, Lin WH, Wang ZX, Yang LP, Zeng ZL, Luo HY. EPHA7 mutation as a predictive biomarker for immune checkpoint inhibitors in multiple cancers. BMC Med 2021; 19:26.
    • POLD1, POLE
    • 4 He J, Ouyang W, Zhao W, Shao L, Li B, Liu B, Wang D, Han-Zhang H, Zhang Z, Shao L, Li W. Distinctive genomic characteristics in POLE/POLD1-mutant cancers can potentially predict beneficial clinical outcomes in patients who receive immune checkpoint inhibitor. Ann Transl Med 2021; 9:129.
    • LRP1B
    • 4 Brown LC, Tucker MD, Sedhom R, Schwartz EB, Zhu J, Kao C, Labriola MK, Gupta RT, Marin D, Wu Y, Gupta S, Zhang T, Harrison MR, George DJ, Alva A, Antonarakis ES, Armstrong AJ. LRP1B mutations are associated with favorable outcomes to immune checkpoint inhibitors across multiple cancer types. J Immunother Cancer 2021; 9(3). pii: e001792.
    • Anti-PD-1 monoclonal antibody + Anti-CTLA-4 monoclonal antibody
    • CDKN2A
    • R2 Adib E, Nassar AH, Akl EW, Abou Alaiwi S, Nuzzo PV, Mouhieddine TH, Sonpavde G, Haddad RI, Mouw KW, Giannakis M, Hodi FS, Shukla SA, Gusev A, Braun DA, Choueiri TK, Kwiatkowski DJ. CDKN2A Alterations and Response to Immunotherapy in Solid Tumors. Clin Cancer Res 2021; 27:4025-4035.
    • ARID2, BRD7, PBRM1
    • 4 Pan D, Kobayashi A, Jiang P, Ferrari de Andrade L, Tay RE, Luoma AM, Tsoucas D, Qiu X, Lim K, Rao P, Long HW, Yuan GC, Doench J, Brown M, Liu XS, Wucherpfennig KW. A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing. Science 2018; 359:770-775.
    • EPHA7
    • 4 Zhang Z, Wu HX, Lin WH, Wang ZX, Yang LP, Zeng ZL, Luo HY. EPHA7 mutation as a predictive biomarker for immune checkpoint inhibitors in multiple cancers. BMC Med 2021; 19:26.
    • Anti-PD-L1 monoclonal antibody
    • EGFR
    • R2 Lee CK, Man J, Lord S, Cooper W, Links M, Gebski V, Herbst RS, Gralla RJ, Mok T, Yang JC. Clinical and Molecular Characteristics Associated With Survival Among Patients Treated With Checkpoint Inhibitors for Advanced Non-Small Cell Lung Carcinoma: A Systematic Review and Meta-analysis. JAMA Oncol 2018; 4:210-216.
    • STK11, STK11+KRAS
    • R2 Skoulidis F, Goldberg ME, Greenawalt DM, Hellmann MD, Awad MM, Gainor JF, Schrock AB, Hartmaier RJ, Trabucco SE, Gay L, Ali SM, Elvin JA, Singal G, Ross JS, Fabrizio D, Szabo PM, Chang H, Sasson A, Srinivasan S, Kirov S, Szustakowski J, Vitazka P, Edwards R, Bufill JA, Sharma N, Ou SI, Peled N, Spigel DR, Rizvi H, Aguilar EJ, Carter BW, Erasmus J, Halpenny DF, Plodkowski AJ, Long NM, Nishino M, Denning WL, Galan-Cobo A, Hamdi H, Hirz T, Tong P, Wang J, Rodriguez-Canales J, Villalobos PA, Parra ER, Kalhor N, Sholl LM, Sauter JL, Jungbluth AA, Mino-Kenudson M, Azimi R, Elamin YY, Zhang J, Leonardi GC, Jiang F, Wong KK, Lee JJ, Papadimitrakopoulou VA, Wistuba II, Miller VA, Frampton GM, Wolchok JD, Shaw AT, Jänne PA, Stephens PJ, Rudin CM, Geese WJ, Albacker LA, Heymach JV. STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS-Mutant Lung Adenocarcinoma. Cancer Discov 2018; 8:822-835.
    • ALK
    • R2 Mazieres J, Drilon A, Lusque A, Mhanna L, Cortot AB, Mezquita L, Thai AA, Mascaux C, Couraud S, Veillon R, Van den Heuvel M, Neal J, Peled N, Früh M, Ng TL, Gounant V, Popat S, Diebold J, Sabari J, Zhu VW, Rothschild SI, Bironzo P, Martinez-Marti A, Curioni-Fontecedro A, Rosell R, Lattuca-Truc M, Wiesweg M, Besse B, Solomon B, Barlesi F, Schouten RD, Wakelee H, Camidge DR, Zalcman G, Novello S, Ou SI, Milia J, Gautschi O. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol 2019; 30:1321-1328.
    • Mismatch repair, Tumour Mutational Burden
    • R2 Touat M, Li YY, Boynton AN, Spurr LF, Iorgulescu JB, Bohrson CL, Cortes-Ciriano I, Birzu C, Geduldig JE, Pelton K, Lim-Fat MJ, Pal S, Ferrer-Luna R, Ramkissoon SH, Dubois F, Bellamy C, Currimjee N, Bonardi J, Qian K, Ho P, Malinowski S, Taquet L, Jones RE, Shetty A, Chow KH, Sharaf R, Pavlick D, Albacker LA, Younan N, Baldini C, Verreault M, Giry M, Guillerm E, Ammari S, Beuvon F, Mokhtari K, Alentorn A, Dehais C, Houillier C, Laigle-Donadey F, Psimaras D, Lee EQ, Nayak L, McFaline-Figueroa JR, Carpentier A, Cornu P, Capelle L, Mathon B, Barnholtz-Sloan JS, Chakravarti A, Bi WL, Chiocca EA, Fehnel KP, Alexandrescu S, Chi SN, Haas-Kogan D, Batchelor TT, Frampton GM, Alexander BM, Huang RY, Ligon AH, Coulet F, Delattre JY, Hoang-Xuan K, Meredith DM, Santagata S, Duval A, Sanson M, Cherniack AD, Wen PY, Reardon DA, Marabelle A, Park PJ, Idbaih A, Beroukhim R, Bandopadhayay P, Bielle F, Ligon KL. Mechanisms and therapeutic implications of hypermutation in gliomas. Nature 2020; 580:517-523.
    • CDKN2A
    • R2 Adib E, Nassar AH, Akl EW, Abou Alaiwi S, Nuzzo PV, Mouhieddine TH, Sonpavde G, Haddad RI, Mouw KW, Giannakis M, Hodi FS, Shukla SA, Gusev A, Braun DA, Choueiri TK, Kwiatkowski DJ. CDKN2A Alterations and Response to Immunotherapy in Solid Tumors. Clin Cancer Res 2021; 27:4025-4035.
    • HLA-A
    • R2 Naranbhai V, Viard M, Dean M, Groha S, Braun DA, Labaki C, Shukla SA, Yuki Y, Shah P, Chin K, Wind-Rotolo M, Mu XJ, Robbins PB, Gusev A, Choueiri TK, Gulley JL, Carrington M. HLA-A*03 and response to immune checkpoint blockade in cancer: an epidemiological biomarker study. Lancet Oncol 2022; 23:172-184.
    • LRP1B
    • 4 Brown LC, Sedhom R, Schwartz EB, Zhu J, Kao C, Tucker MD, Labriola M, Gupta RT, Marin D, Wu Y, Zhang T, Harrison MR, George DJ, Alva AS, Antonarakis ES, Armstrong AJ. Association of LRP1B pathogenic genomic alterations with favorable outcomes with immune checkpoint inhibitors across multiple tumor types. J Clin Oncol 2020; 38(15_suppl): 3007-3007.
    • POLE
    • 4 Garmezy B, Gheeya JS, Thein KZ, Pilie PG, Wang W, Ahnert JR, Shaw KR, Meric-Bernstam F, Yap TA. Correlation of pathogenic POLE mutations with clinical benefit to immune checkpoint inhibitor therapy. J Clin Oncol 2020; 38(15_suppl): 3008-3008.
    • MLH1, MSH2, MSH6, PMS2
    • 4 Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A 1999; 96:8681-6.
    • 4 Rosty C, Clendenning M, Walsh MD, Eriksen SV, Southey MC, Winship IM, Macrae FA, Boussioutas A, Poplawski NK, Parry S, Arnold J, Young JP, Casey G, Haile RW, Gallinger S, Le Marchand L, Newcomb PA, Potter JD, DeRycke M, Lindor NM, Thibodeau SN, Baron JA, Win AK, Hopper JL, Jenkins MA, Buchanan DD; Colon Cancer Family Registry Cohort. Germline mutations in PMS2 and MLH1 in individuals with solitary loss of PMS2 expression in colorectal carcinomas from the Colon Cancer Family Registry Cohort. BMJ Open 2016; 6:e010293.
    • POLE
    • 4 Santin AD, Bellone S, Buza N, Choi J, Schwartz PE, Schlessinger J, Lifton RP. Regression of Chemotherapy-Resistant Polymerase ε (POLE) Ultra-Mutated and MSH6 Hyper-Mutated Endometrial Tumors with Nivolumab. Clin Cancer Res 2016; 22:5682-5687.
    • ARID1A
    • 4 Shen J, Ju Z, Zhao W, Wang L, Peng Y, Ge Z, Nagel ZD, Zou J, Wang C, Kapoor P, Ma X, Ma D, Liang J, Song S, Liu J, Samson LD, Ajani JA, Li GM, Liang H, Shen X, Mills GB, Peng G. ARID1A deficiency promotes mutability and potentiates therapeutic antitumor immunity unleashed by immune checkpoint blockade. Nat Med 2018; 24:556-562.
    • Tumour Mutational Burden
    • 4 Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, Barron DA, Zehir A, Jordan EJ, Omuro A, Kaley TJ, Kendall SM, Motzer RJ, Hakimi AA, Voss MH, Russo P, Rosenberg J, Iyer G, Bochner BH, Bajorin DF, Al-Ahmadie HA, Chaft JE, Rudin CM, Riely GJ, Baxi S, Ho AL, Wong RJ, Pfister DG, Wolchok JD, Barker CA, Gutin PH, Brennan CW, Tabar V, Mellinghoff IK, DeAngelis LM, Ariyan CE, Lee N, Tap WD, Gounder MM, D'Angelo SP, Saltz L, Stadler ZK, Scher HI, Baselga J, Razavi P, Klebanoff CA, Yaeger R, Segal NH, Ku GY, DeMatteo RP, Ladanyi M, Rizvi NA, Berger MF, Riaz N, Solit DB, Chan TA, Morris LGT. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet 2019; 51:202-206.
    • 4 Goodman AM, Sokol ES, Frampton GM, Lippman SM, Kurzrock R. Microsatellite-Stable Tumors with High Mutational Burden Benefit from Immunotherapy. Cancer Immunol Res 2019; 7:1570-1573.
    • POLE
    • 4 Wang F, Zhao Q, Wang YN, Jin Y, He MM, Liu ZX, Xu RH. Evaluation of POLE and POLD1 Mutations as Biomarkers for Immunotherapy Outcomes Across Multiple Cancer Types. JAMA Oncol 2019 Aug 15. [Epub ahead of print]
    • PRKDC
    • 4 Tan KT, Yeh CN, Chang YC, Cheng JH, Fang WL, Yeh YC, Wang YC, Hsu DS, Wu CE, Lai JI, Chang PM, Chen MH, Lu ML, Chen SJ, Chao Y, Hsiao M, Chen MH. PRKDC: new biomarker and drug target for checkpoint blockade immunotherapy. J Immunother Cancer 2020; 8(1). pii: e000485.
    • 4 Chen Y, Li Y, Guan Y, Huang Y, Lin J, Chen L, Li J, Chen G, Pan LK, Xia X, Xu N, Chang L, Guo Z, Pan J, Yi X, Chen C. Prevalence of PRKDC mutations and association with response to immune checkpoint inhibitors in solid tumors. Mol Oncol 2020; 14:2096-2110.
    • EPHA7
    • 4 Zhang Z, Wu HX, Lin WH, Wang ZX, Yang LP, Zeng ZL, Luo HY. EPHA7 mutation as a predictive biomarker for immune checkpoint inhibitors in multiple cancers. BMC Med 2021; 19:26.
    • POLD1, POLE
    • 4 He J, Ouyang W, Zhao W, Shao L, Li B, Liu B, Wang D, Han-Zhang H, Zhang Z, Shao L, Li W. Distinctive genomic characteristics in POLE/POLD1-mutant cancers can potentially predict beneficial clinical outcomes in patients who receive immune checkpoint inhibitor. Ann Transl Med 2021; 9:129.
    • LRP1B
    • 4 Brown LC, Tucker MD, Sedhom R, Schwartz EB, Zhu J, Kao C, Labriola MK, Gupta RT, Marin D, Wu Y, Gupta S, Zhang T, Harrison MR, George DJ, Alva A, Antonarakis ES, Armstrong AJ. LRP1B mutations are associated with favorable outcomes to immune checkpoint inhibitors across multiple cancer types. J Immunother Cancer 2021; 9(3). pii: e001792.
    • Anti-PD-L1 monoclonal antibody + Anti-CTLA-4 monoclonal antibody
    • CDKN2A
    • R2 Adib E, Nassar AH, Akl EW, Abou Alaiwi S, Nuzzo PV, Mouhieddine TH, Sonpavde G, Haddad RI, Mouw KW, Giannakis M, Hodi FS, Shukla SA, Gusev A, Braun DA, Choueiri TK, Kwiatkowski DJ. CDKN2A Alterations and Response to Immunotherapy in Solid Tumors. Clin Cancer Res 2021; 27:4025-4035.
    • Anti-androgen
    • AR
    • R2 Azad AA, Volik SV, Wyatt AW, Haegert A, Le Bihan S, Bell RH, Anderson SA, McConeghy B, Shukin R, Bazov J, Youngren J, Paris P, Thomas G, Small EJ, Wang Y, Gleave ME, Collins CC, Chi KN. Androgen Receptor Gene Aberrations in Circulating Cell-Free DNA: Biomarkers of Therapeutic Resistance in Castration-Resistant Prostate Cancer. Clin Cancer Res 2015; 21:2315-24.
    • R2 Romanel A, Gasi Tandefelt D, Conteduca V, Jayaram A, Casiraghi N, Wetterskog D, Salvi S, Amadori D, Zafeiriou Z, Rescigno P, Bianchini D, Gurioli G, Casadio V, Carreira S, Goodall J, Wingate A, Ferraldeschi R, Tunariu N, Flohr P, De Giorgi U, de Bono JS, Demichelis F, Attard G. Plasma AR and abiraterone-resistant prostate cancer. Sci Transl Med 2015; 7:312re10.
    • Apalutamide
    • AR
    • R2 Korpal M, Korn JM, Gao X, Rakiec DP, Ruddy DA, Doshi S, Yuan J, Kovats SG, Kim S, Cooke VG, Monahan JE, Stegmeier F, Roberts TM, Sellers WR, Zhou W, Zhu P. An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide). Cancer Discov 2013; 3:1030-43.
    • AR, AURKA, MYCN, RB1, TP53
    • R2 Watson PA, Arora VK, Sawyers CL. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nat Rev Cancer 2015; 15:701-11.
    • AR
    • R2 Lallous N, Volik SV, Awrey S, Leblanc E, Tse R, Murillo J, Singh K, Azad AA, Wyatt AW, LeBihan S, Chi KN, Gleave ME, Rennie PS, Collins CC, Cherkasov A. Functional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients. Genome Biol 2016; 17:10.
    • Apatinib + Gefitinib
    • EGFR
    • 2 Zhang L, Zhao H, Zhang Z, Yao W, Min X, Gu K, Yu G, Cheng C, Cui J, Miao L, Song X, Zhang L, Yuan X, Fang Y, Fu X, Hu C, Zhu X, Fan Y, Yu Q. LBA50 ACTIVE: Apatinib plus gefitinib versus placebo plus gefitinib as first-line treatment for advanced epidermal growth factor receptor-mutant (EGFRm) non-small-cell lung cancer (NSCLC): A multicentered, randomized, double-blind, placebo-controlled phase III trial (CTONG1706). Ann Oncol 2020; 31 (4): S1181. 10.1016/j.annonc.2020.08.2283
    • Aromatase Inhibitor
    • ESR1
    • R2 Jeselsohn R, Buchwalter G, De Angelis C, Brown M, Schiff R. ESR1 mutations—a mechanism for acquired endocrine resistance in breast cancer. Nat Rev Clin Oncol 2015; 12:573-83.
    • Arsenic trioxide
    • PTCH1, SMO
    • 4 Kim J, Aftab BT, Tang JY, Kim D, Lee AH, Rezaee M, Kim J, Chen B, King EM, Borodovsky A, Riggins GJ, Epstein EH Jr, Beachy PA, Rudin CM. Itraconazole and arsenic trioxide inhibit Hedgehog pathway activation and tumor growth associated with acquired resistance to smoothened antagonists. Cancer Cell 2013; 23:23-34.
    • Asciminib
    • ABL1
    • R2 Wylie AA, Schoepfer J, Jahnke W, Cowan-Jacob SW, Loo A, Furet P, Marzinzik AL, Pelle X, Donovan J, Zhu W, Buonamici S, Hassan AQ, Lombardo F, Iyer V, Palmer M, Berellini G, Dodd S, Thohan S, Bitter H, Branford S, Ross DM, Hughes TP, Petruzzelli L, Vanasse KG, Warmuth M, Hofmann F, Keen NJ, Sellers WR. The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1. Nature 2017; 543:733-737.
    • R2 Hughes TP, Mauro MJ, Cortes JE, Minami H, Rea D, DeAngelo DJ, Breccia M, Goh YT, Talpaz M, Hochhaus A, le Coutre P, Ottmann O, Heinrich MC, Steegmann JL, Deininger MWN, Janssen JJWM, Mahon FX, Minami Y, Yeung D, Ross DM, Tallman MS, Park JH, Druker BJ, Hynds D, Duan Y, Meille C, Hourcade-Potelleret F, Vanasse KG, Lang F, Kim DW. Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. N Engl J Med 2019; 381:2315-2326.
    • ABL1
    • 3 Wylie AA, Schoepfer J, Jahnke W, Cowan-Jacob SW, Loo A, Furet P, Marzinzik AL, Pelle X, Donovan J, Zhu W, Buonamici S, Hassan AQ, Lombardo F, Iyer V, Palmer M, Berellini G, Dodd S, Thohan S, Bitter H, Branford S, Ross DM, Hughes TP, Petruzzelli L, Vanasse KG, Warmuth M, Hofmann F, Keen NJ, Sellers WR. The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1. Nature 2017; 543:733-737.
    • 3 Hughes TP, Mauro MJ, Cortes JE, Minami H, Rea D, DeAngelo DJ, Breccia M, Goh YT, Talpaz M, Hochhaus A, le Coutre P, Ottmann O, Heinrich MC, Steegmann JL, Deininger MWN, Janssen JJWM, Mahon FX, Minami Y, Yeung D, Ross DM, Tallman MS, Park JH, Druker BJ, Hynds D, Duan Y, Meille C, Hourcade-Potelleret F, Vanasse KG, Lang F, Kim DW. Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. N Engl J Med 2019; 381:2315-2326.
    • Atezolizumab
    • CD274+EGFR+ALK
    • 1B Spigel D, de Marinis F, Giaccone G, Reinmuth N, Vergnenegre A, Barrios CH, Morise M, et al. IMpower110: Interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1?selected NSCLC. Ann Oncol 2019; 30(suppl 5): v915
    • CD274
    • 1B Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 2016; 387:1909-20.
    • CD274+EGFR+ALK
    • 1B Herbst RS, Giaccone G, de Marinis F, Reinmuth N, Vergnenegre A, Barrios CH, Morise M, Felip E, Andric Z, Geater S, Özgüroğlu M, Zou W, Sandler A, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, McCleland M, Mocci S, Jassem J, Spigel DR. Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC. N Engl J Med 2020; 383:1328-1339.
    • EGFR
    • R2 Lee CK, Man J, Lord S, Cooper W, Links M, Gebski V, Herbst RS, Gralla RJ, Mok T, Yang JC. Clinical and Molecular Characteristics Associated With Survival Among Patients Treated With Checkpoint Inhibitors for Advanced Non-Small Cell Lung Carcinoma: A Systematic Review and Meta-analysis. JAMA Oncol 2018; 4:210-216.
    • Microsatellite Instability
    • R2 Eng C, Kim TW, Bendell J, Argilés G, Tebbutt NC, Di Bartolomeo M, Falcone A, Fakih M, Kozloff M, Segal NH, Sobrero A, Yan Y, Chang I, Uyei A, Roberts L, Ciardiello F; IMblaze370 Investigators. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol 2019; 20:849-861.
    • ALK
    • R2 Mazieres J, Drilon A, Lusque A, Mhanna L, Cortot AB, Mezquita L, Thai AA, Mascaux C, Couraud S, Veillon R, Van den Heuvel M, Neal J, Peled N, Früh M, Ng TL, Gounant V, Popat S, Diebold J, Sabari J, Zhu VW, Rothschild SI, Bironzo P, Martinez-Marti A, Curioni-Fontecedro A, Rosell R, Lattuca-Truc M, Wiesweg M, Besse B, Solomon B, Barlesi F, Schouten RD, Wakelee H, Camidge DR, Zalcman G, Novello S, Ou SI, Milia J, Gautschi O. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol 2019; 30:1321-1328.
    • Microsatellite Instability
    • 4 Eng C, Kim TW, Bendell J, Argilés G, Tebbutt NC, Di Bartolomeo M, Falcone A, Fakih M, Kozloff M, Segal NH, Sobrero A, Yan Y, Chang I, Uyei A, Roberts L, Ciardiello F; IMblaze370 Investigators. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol 2019; 20:849-861.
    • ARID1A, CXCL13
    • 4 Goswami S, Chen Y, Anandhan S, Szabo PM, Basu S, Blando JM, Liu W, Zhang J, Natarajan SM, Xiong L, Guan B, Yadav SS, Saci A, Allison JP, Galsky MD, Sharma P. ARID1A mutation plus CXCL13 expression act as combinatorial biomarkers to predict responses to immune checkpoint therapy in mUCC. Sci Transl Med 2020; 12(548). pii: eabc4220.
    • CDK12
    • 4 Schweizer MT, Ha G, Gulati R, Brown LC, McKay RR, Dorff T, Hoge ACH, Reichel J, Vats P, Kilari D, Patel V, Oh WK, Chinnaiyan A, Pritchard CC, Armstrong AJ, Montgomery RB, Alva A. CDK12-Mutated Prostate Cancer: Clinical Outcomes With Standard Therapies and Immune Checkpoint Blockade. JCO Precis Oncol 2020;4:382-392.
    • ARID1A, ARID1B, PBRM1, SMARCA4, SMARCB1
    • 4 Botta GP, Kato S, Patel H, Fanta P, Lee S, Okamura R, Kurzrock R. SWI/SNF complex alterations as a biomarker of immunotherapy efficacy in pancreatic cancer. JCI Insight 2021; 6(18). pii: e150453.
    • Atezolizumab + Carboplatin + Paclitaxel + Bevacizumab
    • CD274
    • 4 Moore KN, Bookman M, Sehouli J, Miller A, Anderson C, Scambia G, Myers T, Taskiran C, Robison K, Mäenpää J, Willmott L, Colombo N, Thomes-Pepin J, Liontos M, Gold MA, Garcia Y, Sharma SK, Darus CJ, Aghajanian C, Okamoto A, Wu X, Safin R, Wu F, Molinero L, Maiya V, Khor VK, Lin YG, Pignata S. Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39). J Clin Oncol 2021 Apr 23:JCO2100306. [Epub ahead of print]
    • Atezolizumab + Cobimetinib
    • Microsatellite Instability
    • R2 Eng C, Kim TW, Bendell J, Argilés G, Tebbutt NC, Di Bartolomeo M, Falcone A, Fakih M, Kozloff M, Segal NH, Sobrero A, Yan Y, Chang I, Uyei A, Roberts L, Ciardiello F; IMblaze370 Investigators. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol 2019; 20:849-861.
    • Atezolizumab + Cobimetinib + Vemurafenib
    • BRAF
    • 2 Sullivan RJ, Hamid O, Gonzalez R, Infante JR, Patel MR, Hodi FS, Lewis KD, Tawbi HA, Hernandez G, Wongchenko MJ, Chang Y, Roberts L, Ballinger M, Yan Y, Cha E, Hwu P. Atezolizumab plus cobimetinib and vemurafenib in BRAF-mutated melanoma patients. Nat Med 2019; 25:929-935.
    • 2 Gutzmer R, Stroyakovskiy D, Gogas H, Robert C, Lewis K, Protsenko S, Pereira RP, Eigentler T, Rutkowski P, Demidov L, Manikhas GM, Yan Y, Huang KC, Uyei A, McNally V, McArthur GA, Ascierto PA. Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAFV600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2020; 395:1835-1844.
    • Atezolizumab + Nab-paclitaxel
    • Molecular subtype, Tumour microenvironment
    • 4 Emens LA, Goldstein LD, Schmid P, Rugo HS, Adams S, Barrios CH, Schneeweiss A, Dieras V, Iwata H, Chang C, Koeppen H, Chui SY, Loi S, Molinero L. The tumor microenvironment (TME) and atezolizumab + nab-paclitaxel (A+nP) activity in metastatic triple-negative breast cancer (mTNBC): IMpassion130. J Clin Oncol 2021; 39(15_suppl): 1006-1006.
    • Atezolizumab + Tiragolumab
    • CD274
    • Atezolizumab + Vemurafenib + Cobimetinib
    • BRAF
    • 2 Gutzmer R, Stroyakovskiy D, Gogas H, Robert C, Lewis K, Protsenko S, Pereira RP, Eigentler T, Rutkowski P, Demidov L, Manikhas GM, Yan Y, Huang KC, Uyei A, McNally V, McArthur GA, Ascierto PA. Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAFV600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2020; 395:1835-1844.
    • Atezolizumab + nab-Paclitaxel
    • CD274
    • 1B Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Hegg R, Im SA, Shaw Wright G, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA; IMpassion130 Trial Investigators. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med 2018; 379:2108-2121.
    • 1B Miles D, Gligorov J, André F, Cameron D, Schneeweiss A, Barrios C, Xu B, Wardley A, Kaen D, Andrade L, Semiglazov V, Reinisch M, Patel S, Patre M, Morales L, Patel SL, Kaul M, Barata T, O'Shaughnessy J; IMpassion131 investigators. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol 2021; 32:994-1004.
    • Avapritinib
    • KIT
    • R2 Gajiwala KS, Wu JC, Christensen J, Deshmukh GD, Diehl W, DiNitto JP, English JM, Greig MJ, He YA, Jacques SL, Lunney EA, McTigue M, Molina D, Quenzer T, Wells PA, Yu X, Zhang Y, Zou A, Emmett MR, Marshall AG, Zhang HM, Demetri GD. KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. Proc Natl Acad Sci U S A 2009; 106:1542-7.
    • R2 Hemming ML, Heinrich MC, Bauer S, George S. Translational insights into gastrointestinal stromal tumor and current clinical advances. Ann Oncol 2018; 29:2037-2045.
    • R2 Serrano C, Mariño-Enríquez A, Tao DL, Ketzer J, Eilers G, Zhu M, Yu C, Mannan AM, Rubin BP, Demetri GD, Raut CP, Presnell A, McKinley A, Heinrich MC, Czaplinski JT, Sicinska E, Bauer S, George S, Fletcher JA. Complementary activity of tyrosine kinase inhibitors against secondary kit mutations in imatinib-resistant gastrointestinal stromal tumours. Br J Cancer 2019; 120:612-620.
    • R2 Smith BD, Kaufman MD, Lu WP, Gupta A, Leary CB, Wise SC, Rutkoski TJ, Ahn YM, Al-Ani G, Bulfer SL, Caldwell TM, Chun L, Ensinger CL, Hood MM, McKinley A, Patt WC, Ruiz-Soto R, Su Y, Telikepalli H, Town A, Turner BA, Vogeti L, Vogeti S, Yates K, Janku F, Abdul Razak AR, Rosen O, Heinrich MC, Flynn DL. Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants. Cancer Cell 2019; 35:738-751.e9.
    • R2 Serrano C, Mariño-Enríquez A, Tao DL, Ketzer J, Eilers G, Zhu M, Yu C, Mannan AM, Rubin BP, Demetri GD, Raut CP, Presnell A, McKinley A, Heinrich MC, Czaplinski JT, Sicinska E, Bauer S, George S, Fletcher JA. Correction: Complementary activity of tyrosine kinase inhibitors against secondary kit mutations in imatinib-resistant gastrointestinal stromal tumours. Br J Cancer 2019; 121:281.
    • R2 Apsel Winger B, Cortopassi WA, Garrido Ruiz D, Ding L, Jang K, Leyte-Vidal A, Zhang N, Esteve-Puig R, Jacobson MP, Shah NP. ATP-Competitive Inhibitors Midostaurin and Avapritinib Have Distinct Resistance Profiles in Exon 17-Mutant KIT. Cancer Res 2019; 79:4283-4292.
    • KIT
    • 2 Jason R. Gotlib, Deepti Radia, Daniel J. DeAngelo, Prithviraj Bose, Mark W Drummond, Elizabeth O. Hexner, William A Robinson, Maureen G. Conlan, Ronny G. Oren, Hongliang Shi, Michael W. Deininger; Avapritinib, a Potent and Selective Inhibitor of KIT D816V, Improves Symptoms of Advanced Systemic Mastocytosis (AdvSM): Analyses of Patient Reported Outcomes (PROs) from the Phase 1 (EXPLORER) Study Using the (AdvSM) Symptom Assessment Form (AdvSM-SAF), a New PRO Questionnaire for (AdvSM). Blood 2018; 132 (Supplement 1): 351. doi: https://doi.org/10.1182/blood-2018-99-112017
    • PDGFRA
    • 2 Heinrich MC, Jones RL, Mehren Mv, Bauer S, Kang Y, Schoffski P, Eskens F, Mir O, Cassier PA, Serrano C, Tap WD, Trent JC, Rutkowski P, Patel S, Chawla SP, Meiri E, Zhou T, Mamlouk KK, Roche M, George S, MA SORCSMCCTCoANGBMCMDCIMSB. Clinical activity of avapritinib in ≥ fourth-line (4L+) and PDGFRA Exon 18 gastrointestinal stromal tumors (GIST). J Clin Oncol 2019; 37(15_suppl): 11022-11022.
    • 2 Heinrich MC, Jones RL, von Mehren M, Schöffski P, Serrano C, Kang YK, Cassier PA, Mir O, Eskens F, Tap WD, Rutkowski P, Chawla SP, Trent J, Tugnait M, Evans EK, Lauz T, Zhou T, Roche M, Wolf BB, Bauer S, George S. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial. Lancet Oncol 2020; 21:935-946.
    • KIT
    • 3 Evans EK, Gardino AK, Kim JL, Hodous BL, Shutes A, Davis A, Zhu XJ, Schmidt-Kittler O, Wilson D, Wilson K, DiPietro L, Zhang Y, Brooijmans N, LaBranche TP, Wozniak A, Gebreyohannes YK, Schöffski P, Heinrich MC, DeAngelo DJ, Miller S, Wolf B, Kohl N, Guzi T, Lydon N, Boral A, Lengauer C. A precision therapy against cancers driven by KIT/PDGFRA mutations. Sci Transl Med 2017; 9(414). pii: eaao1690.
    • 3 Kang YK, George S, Jones RL, Rutkowski P, Shen L, Mir O, Patel S, Zhou Y, von Mehren M, Hohenberger P, Villalobos V, Brahmi M, Tap WD, Trent J, Pantaleo MA, Schöffski P, He K, Hew P, Newberry K, Roche M, Heinrich MC, Bauer S. Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study. J Clin Oncol 2021 Aug 3:JCO2100217. [Epub ahead of print]
    • Avelumab
    • HLA-A
    • R2 Naranbhai V, Viard M, Dean M, Groha S, Braun DA, Labaki C, Shukla SA, Yuki Y, Shah P, Chin K, Wind-Rotolo M, Mu XJ, Robbins PB, Gusev A, Choueiri TK, Gulley JL, Carrington M. HLA-A*03 and response to immune checkpoint blockade in cancer: an epidemiological biomarker study. Lancet Oncol 2022; 23:172-184.
    • CD274
    • 2 Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulović S, Demey W, Ullén A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte R, Wang J, Huang B, Davis C, Fowst C, Costa N, Blake-Haskins JA, di Pietro A, Grivas P. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med 2020 Sep 18. [Epub ahead of print]
    • Avelumab + Axitinib
    • HLA-A
    • R2 Naranbhai V, Viard M, Dean M, Groha S, Braun DA, Labaki C, Shukla SA, Yuki Y, Shah P, Chin K, Wind-Rotolo M, Mu XJ, Robbins PB, Gusev A, Choueiri TK, Gulley JL, Carrington M. HLA-A*03 and response to immune checkpoint blockade in cancer: an epidemiological biomarker study. Lancet Oncol 2022; 23:172-184.
    • Axitinib
    • KIT
    • R2 Liu F, Zou F, Chen C, Yu K, Liu X, Qi S, Wu J, Hu C, Hu Z, Liu J, Liu X, Wang L, Ge J, Wang W, Ren T, Bai M, Cai Y, Xiao X, Qian F, Tang J, Liu Q, Liu J. Axitinib overcomes multiple imatinib resistant cKIT mutations including the gatekeeper mutation T670I in gastrointestinal stromal tumors. Ther Adv Med Oncol 2019; 11:1758835919849757. eCollection 2019.
    • KIT
    • 4 Liu F, Zou F, Chen C, Yu K, Liu X, Qi S, Wu J, Hu C, Hu Z, Liu J, Liu X, Wang L, Ge J, Wang W, Ren T, Bai M, Cai Y, Xiao X, Qian F, Tang J, Liu Q, Liu J. Axitinib overcomes multiple imatinib resistant cKIT mutations including the gatekeeper mutation T670I in gastrointestinal stromal tumors. Ther Adv Med Oncol 2019; 11:1758835919849757. eCollection 2019.
    • Azacitidine + Venetoclax
    • IDH1, IDH2
    • 3 DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Döhner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hájek R, Porkka K, Illés Á, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med 2020; 383:617-629.
    • anti-ERBB2 monoclonal antibody
    • ERBB2
    • 4 My Pathway: A Study Evaluating Herceptin/Perjeta, Tarceva, Zelboraf/Cotellic, Erivedge, Alecensa, and Tecentriq Treatment Targeted Against Certain Molecular Alterations in Participants With Advanced Solid Tumors [NCT02091141]
    • 4 Hainsworth JD, Meric-Bernstam F, Swanton C, Hurwitz H, Spigel DR, Sweeney C, Burris H, Bose R, Yoo B, Stein A, Beattie M, Kurzrock R. Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study. J Clin Oncol 2018; 36:536-542.
    • B
    • BAY-1895344
    • ATM
    • 4 Yap TA, Tan DSP, Terbuch A, Caldwell R, Guo C, Goh BC, Heong V, Haris NRM, Bashir S, Drew Y, Hong DS, Meric-Bernstam F, Wilkinson G, Hreiki J, Wengner AM, Bladt F, Schlicker A, Ludwig M, Zhou Y, Liu L, Bordia S, Plummer R, Lagkadinou E, de Bono JS. First-in-Human Trial of the Oral Ataxia Telangiectasia and RAD3-Related (ATR) Inhibitor BAY 1895344 in Patients with Advanced Solid Tumors. Cancer Discov 2021; 11:80-91.
    • BAY2010112
    • PSMA
    • 4 Friedrich M, Raum T, Lutterbuese R, Voelkel M, Deegen P, Rau D, Kischel R, Hoffmann P, Brandl C, Schuhmacher J, Mueller P, Finnern R, Fuergut M, Zopf D, Slootstra JW, Baeuerle PA, Rattel B, Kufer P. Regression of human prostate cancer xenografts in mice by AMG 212/BAY2010112, a novel PSMA/CD3-Bispecific BiTE antibody cross-reactive with non-human primate antigens. Mol Cancer Ther 2012; 11:2664-73.
    • 4 Patterson JT, Isaacson J, Kerwin L, Atassi G, Duggal R, Bresson D, Zhu T, Zhou H, Fu Y, Kaufmann GF. PSMA-targeted bispecific Fab conjugates that engage T cells. Bioorg Med Chem Lett 2017; 27:5490-5495.
    • BCL6 inhibitor
    • BCL6
    • 4 Logarajah S, Hunter P, Kraman M, Steele D, Lakhani S, Bobrow L, Venkitaraman A, Wagner S. BCL-6 is expressed in breast cancer and prevents mammary epithelial differentiation. Oncogene 2003; 22:5572-8.
    • 4 Cerchietti LC, Yang SN, Shaknovich R, Hatzi K, Polo JM, Chadburn A, Dowdy SF, Melnick A. A peptomimetic inhibitor of BCL6 with potent antilymphoma effects in vitro and in vivo. Blood 2009; 113:3397-405.
    • 4 Cardenas MG, Yu W, Beguelin W, Teater MR, Geng H, Goldstein RL, Oswald E, Hatzi K, Yang SN, Cohen J, Shaknovich R, Vanommeslaeghe K, Cheng H, Liang D, Cho HJ, Abbott J, Tam W, Du W, Leonard JP, Elemento O, Cerchietti L, Cierpicki T, Xue F, MacKerell AD Jr, Melnick AM. Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma. J Clin Invest 2016; 126:3351-62.
    • BET inhibitor
    • MYCN
    • 4 Puissant A, Frumm SM, Alexe G, Bassil CF, Qi J, Chanthery YH, Nekritz EA, Zeid R, Gustafson WC, Greninger P, Garnett MJ, McDermott U, Benes CH, Kung AL, Weiss WA, Bradner JE, Stegmaier K. Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov 2013; 3:308-23.
    • PBRM1
    • 4 Morel D, Almouzni G, Soria JC, Postel-Vinay S. Targeting chromatin defects in selected solid tumors based on oncogene addiction, synthetic lethality and epigenetic antagonism. Ann Oncol 2017; 28:254-269.
    • BRD2, BRD3, BRD4, BRDT, MYC, MYCN, SMARCA4
    • 4 Cochran AG, Conery AR, Sims RJ 3rd. Bromodomains: a new target class for drug development. Nat Rev Drug Discov 2019; 18:609-628.
    • BGB3245
    • BRAF
    • R2 Wang J, Yao Z, Jonsson P, Allen AN, Qin ACR, Uddin S, Dunkel IJ, Petriccione M, Manova K, Haque S, Rosenblum MK, Pisapia DJ, Rosen N, Taylor BS, Pratilas CA. A Secondary Mutation in BRAF Confers Resistance to RAF Inhibition in a BRAFV600E-Mutant Brain Tumor. Cancer Discov 2018; 8:1130-1141.
    • BGB659
    • BRAF
    • 4 Yao Z, Gao Y, Su W, Yaeger R, Tao J, Na N, Zhang Y, Zhang C, Rymar A, Tao A, Timaul NM, Mcgriskin R, Outmezguine NA, Zhao H, Chang Q, Qeriqi B, Barbacid M, de Stanchina E, Hyman DM, Bollag G, Rosen N. RAF inhibitor PLX8394 selectively disrupts BRAF dimers and RAS-independent BRAF-mutant-driven signaling. Nat Med 2019; 25:284-291.
    • BI907828
    • MDM2+TP53
    • 3 LoRusso P, Gounder MM, Patel MR, Yamamoto N, Bauer TM, Laurie S, Grempler R, Davenport T, Geng J, Rohrbacher M, Lahmar M. A phase I dose-escalation study of the MDM2-p53 antagonist BI 907828 in patients (pts) with advanced solid tumors. J Clin Oncol 2021; 39(15_suppl): 3016-3016.
    • 3 Gounder MM, Yamamoto N, Patel MR, Bauer TM, Schöffski P, Grempler R, Durland-Busbice S, Geng J, Maerten A, LoRusso P. A phase Ia/Ib, dose-escalation/expansion study of the MDM2–p53 antagonist BI 907828 in patients with solid tumors, including advanced/metastatic liposarcoma (LPS). J Clin Oncol 2022; 40(16_suppl): 3004-3004.
    • BMS-754807
    • IRS2+BRAF, IRS2+KRAS
    • R2 Huang F, Chang H, Greer A, Hillerman S, Reeves KA, Hurlburt W, Cogswell J, Patel D, Qi Z, Fairchild C, Ryseck RP, Wong TW, Finckenstein FG, Jackson J, Carboni JM. IRS2 copy number gain, KRAS and BRAF mutation status as predictive biomarkers for response to the IGF-1R/IR inhibitor BMS-754807 in colorectal cancer cell lines. Mol Cancer Ther 2015; 14:620-30.
    • IRS2
    • 4 Huang F, Chang H, Greer A, Hillerman S, Reeves KA, Hurlburt W, Cogswell J, Patel D, Qi Z, Fairchild C, Ryseck RP, Wong TW, Finckenstein FG, Jackson J, Carboni JM. IRS2 copy number gain, KRAS and BRAF mutation status as predictive biomarkers for response to the IGF-1R/IR inhibitor BMS-754807 in colorectal cancer cell lines. Mol Cancer Ther 2015; 14:620-30.
    • BOS172738
    • RET
    • 3 Schoffski P, Cho BC, Italiano A, Loong HHF, Massard C, Rodriguez LM, Shih J, Subbiah V, Verlingue L, Andreas K, Basson CT, Clawson A, Ho PT, Knight S, Scheuber A, Keegan M. BOS172738, a highly potent and selective RET inhibitor, for the treatment of RET-altered tumors including RET-fusion+ NSCLC and RET-mutant MTC: Phase 1 study results. J Clin Oncol 2021; 39(15_suppl): 3008-3008.
    • BTRC4017A
    • ERBB2
    • 4 A Phase I Study of BTRC4017A in Participants With Locally Advanced or Metastatic HER2-Expressing Cancers [NCT03448042]
    • Balstilimab + Zalifrelimab
    • CD274
    • 3 O'Malley DM, Neffa M, Monk BJ, Melkadze T, Huang M, Kryzhanivska A, Bulat I, Meniawy TM, Bagameri A, Wang EW, Doger de Speville Uribe B, Hegg R, Ortuzar Feliu W, Ancukiewicz M, Lugowska I. Dual PD-1 and CTLA-4 Checkpoint Blockade Using Balstilimab and Zalifrelimab Combination as Second-Line Treatment for Advanced Cervical Cancer: An Open-Label Phase II Study. J Clin Oncol 2022; 40:762-771.
    • Belantamab mafodotin
    • TNFRSF17
    • 3 Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, Abdallah AO, Callander N, Lendvai N, Sborov D, Suvannasankha A, Weisel K, Karlin L, Libby E, Arnulf B, Facon T, Hulin C, Kortüm KM, Rodríguez-Otero P, Usmani SZ, Hari P, Baz R, Quach H, Moreau P, Voorhees PM, Gupta I, Hoos A, Zhi E, Baron J, Piontek T, Lewis E, Jewell RC, Dettman EJ, Popat R, Esposti SD, Opalinska J, Richardson P, Cohen AD. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol 2020; 21:207-221.
    • Belvarafenib
    • ARAF
    • R2 Yen I, Shanahan F, Lee J, Hong YS, Shin SJ, Moore AR, Sudhamsu J, Chang MT, Bae I, Dela Cruz D, Hunsaker T, Klijn C, Liau NPD, Lin E, Martin SE, Modrusan Z, Piskol R, Segal E, Venkatanarayan A, Ye X, Yin J, Zhang L, Kim JS, Lim HS, Kim KP, Kim YJ, Han HS, Lee SJ, Kim ST, Jung M, Hong YH, Noh YS, Choi M, Han O, Nowicka M, Srinivasan S, Yan Y, Kim TW, Malek S. ARAF mutations confer resistance to the RAF inhibitor belvarafenib in melanoma. Nature 2021 May 5. [Epub ahead of print]
    • BRAF
    • 4 Tumor-Agnostic Precision Immuno-Oncology and Somatic Targeting Rational for You (TAPISTRY) Platform Study [NCT04589845]
    • ARAF, BRAF, NRAS
    • 4 Yen I, Shanahan F, Lee J, Hong YS, Shin SJ, Moore AR, Sudhamsu J, Chang MT, Bae I, Dela Cruz D, Hunsaker T, Klijn C, Liau NPD, Lin E, Martin SE, Modrusan Z, Piskol R, Segal E, Venkatanarayan A, Ye X, Yin J, Zhang L, Kim JS, Lim HS, Kim KP, Kim YJ, Han HS, Lee SJ, Kim ST, Jung M, Hong YH, Noh YS, Choi M, Han O, Nowicka M, Srinivasan S, Yan Y, Kim TW, Malek S. ARAF mutations confer resistance to the RAF inhibitor belvarafenib in melanoma. Nature 2021 May 5. [Epub ahead of print]
    • Belvarafenib + Cobimetinib
    • NRAS
    • 3 Shin SJ, Lee J, Kim TM, Kim J, Kim YJ, Hong YS, Kim SY, Kim JE, Lee DH, Hong Y, Noh YS, Kim S, Baek E, Jung S, Rhee P, Kim J, Eng-Wong J, Malhi V, Monemi S, Kim TW, Development KDoCRa, Co. HP, Ltd. , Seoul , Development SKDoCRa, Co. HP, Ltd. , Seoul , Development SKDoEC, Genentech , Inc. , Francisco SS, Pharmacology CDoC, Inc. G, Francisco SS, Safety CDoED, Inc. G, Francisco SS, CA . A phase Ib trial of belvarafenib in combination with cobimetinib in patients with advanced solid tumors: Interim results of dose-escalation and patients with NRAS-mutant melanoma of dose-expansion. J Clin Oncol 2021; 39(15_suppl): 3007-3007.
    • Belzutifan
    • VHL
    • 2 Srinivasan R, Donskov F, Iliopoulos O, Rathmell WK, Narayan V, Maughan BL, Oudard S, Else T, Maranchie JK, Welsh SJ, Roy A, Liu Y, Perini RF, Linehan WM, Jonasch E. Phase 2 study of belzutifan (MK-6482), an oral hypoxia-inducible factor 2α (HIF-2α) inhibitor, for Von Hippel-Lindau (VHL) disease-associated clear cell renal cell carcinoma (ccRCC). J Clin Oncol 2021; 39(15_suppl): 4555-4555.
    • 2 Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan VK, Maughan BL, Oudard S, Else T, Maranchie JK, Welsh SJ, Thamake S, Park EK, Perini RF, Linehan WM, Srinivasan R; MK-6482-004 Investigators. Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease. N Engl J Med 2021; 385:2036-2046.
    • VHL
    • 3 Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan V, Maughan BL, Oudard S, Else T, Maranchie JK, Welsh SJ, Thamake S, Park EK, Zojwalla NJ, Perini RF, Linehan WM, Srinivasan R. Phase II study of the oral HIF-2α inhibitor MK-6482 for Von Hippel-Lindau disease–associated renal cell carcinoma. J Clin Oncol 2020; 38(15_suppl): 5003-5003.
    • 3 Srinivasan R, Donskov F, Iliopoulos O, Rathmell WK, Narayan V, Maughan BL, Oudard S, Else T, Maranchie JK, Welsh SJ, Roy A, Liu Y, Perini RF, Linehan WM, Jonasch E. Phase 2 study of belzutifan (MK-6482), an oral hypoxia-inducible factor 2α (HIF-2α) inhibitor, for Von Hippel-Lindau (VHL) disease-associated clear cell renal cell carcinoma (ccRCC). J Clin Oncol 2021; 39(15_suppl): 4555-4555.
    • 3 Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan VK, Maughan BL, Oudard S, Else T, Maranchie JK, Welsh SJ, Thamake S, Park EK, Perini RF, Linehan WM, Srinivasan R; MK-6482-004 Investigators. Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease. N Engl J Med 2021; 385:2036-2046.
    • VHL
    • 4 Choueiri TK, Bauer TM, Papadopoulos KP, Plimack ER, Merchan JR, McDermott DF, Michaelson MD, Appleman LJ, Thamake S, Perini RF, Zojwalla NJ, Jonasch E. Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis. Nat Med 2021; 27:802-805.
    • EPAS1
    • 4 Kamihara J, Hamilton KV, Pollard JA, Clinton CM, Madden JA, Lin J, Imamovic A, Wall CB, Wassner AJ, Weil BR, Heeney MM, Vargas SO, Kaelin WG Jr, Janeway KA, Perini RF, Zojwalla NJ, Voss SD, DuBois SG. Belzutifan, a Potent HIF2α Inhibitor, in the Pacak-Zhuang Syndrome. N Engl J Med 2021; 385:2059-2065.
    • Bemarituzumab
    • FGFR2
    • 4 Catenacci DVT, Rasco D, Lee J, Rha SY, Lee KW, Bang YJ, Bendell J, Enzinger P, Marina N, Xiang H, Deng W, Powers J, Wainberg ZA. Phase I Escalation and Expansion Study of Bemarituzumab (FPA144) in Patients With Advanced Solid Tumors and FGFR2b-Selected Gastroesophageal Adenocarcinoma. J Clin Oncol 2020; 38:2418-2426.
    • Berzosertib
    • POLD1
    • 4 Hocke S, Guo Y, Job A, Orth M, Ziesch A, Lauber K, De Toni EN, Gress TM, Herbst A, Göke B, Gallmeier E. A synthetic lethal screen identifies ATR-inhibition as a novel therapeutic approach for POLD1-deficient cancers. Oncotarget 2016; 7:7080-95.
    • PBRM1
    • 4 Chabanon RM, Morel D, Eychenne T, Colmet-Daage L, Bajrami I, Dorvault N, Garrido M, Meisenberg C, Lamb A, Ngo C, Hopkins SR, Roumeliotis TI, Jouny S, Hénon C, Kawai-Kawachi A, Astier C, Konde A, Del Nery E, Massard C, Pettitt SJ, Margueron R, Choudhary JS, Almouzni G, Soria JC, Deutsch E, Downs JA, Lord CJ, Postel-Vinay S. PBRM1 Deficiency Confers Synthetic Lethality to DNA Repair Inhibitors in Cancer. Cancer Res 2021 Apr 22. [Epub ahead of print]
    • Berzosertib + Irinotecan
    • ATM
    • 4 Villaruz LC, Kelly K, Waqar SN, Davis EJ, Shapiro G, LoRusso P, Dees EC, Normolle DP, Rhee JC, Chu E, Gore S, Beumer JH. NCI 9938: Phase I clinical trial of ATR inhibitor berzosertib (M6620, VX-970) in combination with irinotecan in patients with advanced solid tumors. J Clin Oncol 2022; 40(16_suppl): 3012-3012.
    • Berzosertib + PF-477736
    • CHEK1
    • 4 Doerr F, George J, Schmitt A, Beleggia F, Rehkämper T, Hermann S, Walter V, Weber JP, Thomas RK, Wittersheim M, Büttner R, Persigehl T, Reinhardt HC. Targeting a non-oncogene addiction to the ATR/CHK1 axis for the treatment of small cell lung cancer. Sci Rep 2017; 7:15511.
    • Bevacizumab + erlotinib
    • FH
    • 3 Srinivasan R, Gurram S, Harthy MA, Singer EA, Sidana A, Shuch BM, Ball MW, Friend JC, Mac L, Purcell E, Vocke C, Kong HH, Cowen EW, Choyke PL, Malayeri AA, Long L, Shih JH, Merino MJ, Linehan WM. Results from a phase II study of bevacizumab and erlotinib in subjects with advanced hereditary leiomyomatosis and renal cell cancer (HLRCC) or sporadic papillary renal cell cancer. J Clin Oncol 2020; 38(15_suppl): 5004-5004.
    • Bicalutamide
    • AR
    • R2 Lallous N, Volik SV, Awrey S, Leblanc E, Tse R, Murillo J, Singh K, Azad AA, Wyatt AW, LeBihan S, Chi KN, Gleave ME, Rennie PS, Collins CC, Cherkasov A. Functional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients. Genome Biol 2016; 17:10.
    • AR
    • 3 Dalin MG, Watson PA, Ho AL, Morris LG. Androgen Receptor Signaling in Salivary Gland Cancer. Cancers (Basel) 2017; 9(2). pii: E17.
    • 3 Fushimi C, Tada Y, Takahashi H, Nagao T, Ojiri H, Masubuchi T, Matsuki T, Miura K, Kawakita D, Hirai H, Hoshino E, Kamata S, Saotome T. A prospective phase II study of combined androgen blockade in patients with androgen receptor-positive metastatic or locally advanced unresectable salivary gland carcinoma. Ann Oncol 2018; 29:979-984.
    • Binimetinib
    • NRAS
    • R2 Cleary JM, Wang V, Heist RS, Kopetz ES, Mitchell EP, Zwiebel JA, Kapner KS, Chen HX, Li S, Gray RJ, McShane LM, Rubinstein LV, Patton DR, Meric-Bernstam F, Dillmon MS, Williams PM, Hamilton SR, Conley BA, Aguirre AJ, O'Dwyer PJ, Harris LN, Arteaga CL, Chen AP, Flaherty KT. Differential Outcomes in Codon 12/13 and Codon 61 NRAS-Mutated Cancers in the Phase II NCI-MATCH Trial of Binimetinib in Patients with NRAS-Mutated Tumors. Clin Cancer Res 2021; 27:2996-3004.
    • NRAS
    • 3 Dummer R, Schadendorf D, Ascierto PA, Arance A, Dutriaux C, Di Giacomo AM, Rutkowski P, Del Vecchio M, Gutzmer R, Mandala M, Thomas L, Demidov L, Garbe C, Hogg D, Liszkay G, Queirolo P, Wasserman E, Ford J, Weill M, Sirulnik LA, Jehl V, Bozón V, Long GV, Flaherty K. Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2017; 18:435-445.
    • 3 Goldinger SM, Valeska Matter A, Urner-Bloch U, Narainsing J, Micaletto S, Blume I, Mangana J, Dummer R. Binimetinib in heavily pretreated patients with NRAS-mutant melanoma with brain metastases. Br J Dermatol 2020; 182:488-490.
    • KRAS
    • 3 Monk BJ, Grisham RN, Banerjee S, Kalbacher E, Mirza MR, Romero I, Vuylsteke P, Coleman RL, Hilpert F, Oza AM, Westermann A, Oehler MK, Pignata S, Aghajanian C, Colombo N, Drill E, Cibula D, Moore KN, Christy-Bittel J, Del Campo JM, Berger R, Marth C, Sehouli J, O'Malley DM, Churruca C, Boyd AP, Kristensen G, Clamp A, Ray-Coquard I, Vergote I. MILO/ENGOT-ov11: Binimetinib Versus Physician's Choice Chemotherapy in Recurrent or Persistent Low-Grade Serous Carcinomas of the Ovary, Fallopian Tube, or Primary Peritoneum. J Clin Oncol 2020 Aug 21:JCO2001164. [Epub ahead of print]
    • KRAS
    • 4 Bendell JC, Javle M, Bekaii-Saab TS, Finn RS, Wainberg ZA, Laheru DA, Weekes CD, Tan BR, Khan GN, Zalupski MM, Infante JR, Jones S, Papadopoulos KP, Tolcher AW, Chavira RE, Christy-Bittel JL, Barrett E, Patnaik A. A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor. Br J Cancer 2017; 116:575-583.
    • 4 Monk BJ, Grisham RN, Banerjee S, Kalbacher E, Mirza MR, Romero I, Vuylsteke P, Coleman RL, Hilpert F, Oza AM, Westermann A, Oehler MK, Pignata S, Aghajanian C, Colombo N, Drill E, Cibula D, Moore KN, Christy-Bittel J, Del Campo JM, Berger R, Marth C, Sehouli J, O'Malley DM, Churruca C, Boyd AP, Kristensen G, Clamp A, Ray-Coquard I, Vergote I. MILO/ENGOT-ov11: Binimetinib Versus Physician's Choice Chemotherapy in Recurrent or Persistent Low-Grade Serous Carcinomas of the Ovary, Fallopian Tube, or Primary Peritoneum. J Clin Oncol 2020 Aug 21:JCO2001164. [Epub ahead of print]
    • Binimetinib + Encorafenib
    • KRAS
    • R2 Ahronian LG, Sennott EM, Van Allen EM, Wagle N, Kwak EL, Faris JE, Godfrey JT, Nishimura K, Lynch KD, Mermel CH, Lockerman EL, Kalsy A, Gurski JM Jr, Bahl S, Anderka K, Green LM, Lennon NJ, Huynh TG, Mino-Kenudson M, Getz G, Dias-Santagata D, Iafrate AJ, Engelman JA, Garraway LA, Corcoran RB. Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations. Cancer Discov 2015; 5:358-67.
    • BRAF
    • 1 Dummer R, Flaherty K, Robert C, Arance AM, Groot JWd, Garbe C, Gogas H, Gutzmer R, Krajsová I, Liszkay G, Loquai C, Mandalà M, Schadendorf D, Yamazaki N, Pickard MD, Zohren F, Edwards ML, Ascierto PA. Five-year overall survival (OS) in COLUMBUS: A randomized phase 3 trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients (pts) with BRAF V600-mutant melanoma. J Clin Oncol 2021; 39(15_suppl): 9507-9507.
    • 1 Dummer R, Ascierto PA, Gogas HJ, Arance A, Mandala M, Liszkay G, Garbe C, Schadendorf D, Krajsova I, Gutzmer R, Chiarion Sileni V, Dutriaux C, de Groot JWB, Yamazaki N, Loquai C, Moutouh-de Parseval LA, Pickard MD, Sandor V, Robert C, Flaherty KT. Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2018; 19:1315-1327.
    • Binimetinib + Encorafenib + Cetuximab
    • BRAF
    • 2 Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, Wasan H, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Pfeiffer P, Orlov S, Lonardi S, Elez E, Kim TW, Schellens JHM, Guo C, Krishnan A, Dekervel J, Morris V, Calvo Ferrandiz A, Tarpgaard LS, Braun M, Gollerkeri A, Keir C, Maharry K, Pickard M, Christy-Bittel J, Anderson L, Sandor V, Tabernero J. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. N Engl J Med 2019; 381:1632-1643.
    • 2 Tabernero J, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, Desai J, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Elez E, Gollerkeri A, Maharry K, Christy-Bittel J, Kopetz S. Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study. J Clin Oncol 2021; 39:273-284.
    • Birabresib
    • BRD4
    • 4 Stathis A, Zucca E, Bekradda M, Gomez-Roca C, Delord JP, de La Motte Rouge T, Uro-Coste E, de Braud F, Pelosi G, French CA. Clinical Response of Carcinomas Harboring the BRD4-NUT Oncoprotein to the Targeted Bromodomain Inhibitor OTX015/MK-8628. Cancer Discov 2016; 6:492-500.
    • BRD3, BRD4, NUTM1
    • 4 Lewin J, Soria JC, Stathis A, Delord JP, Peters S, Awada A, Aftimos PG, Bekradda M, Rezai K, Zeng Z, Hussain A, Perez S, Siu LL, Massard C. Phase Ib Trial With Birabresib, a Small-Molecule Inhibitor of Bromodomain and Extraterminal Proteins, in Patients With Selected Advanced Solid Tumors. J Clin Oncol 2018; 36:3007-3014.
    • Bispecific PSMA/CD3 antibody
    • PSMA
    • 4 Chiu D, Tavaré R, Haber L, Aina OH, Vazzana K, Ram P, Danton M, Finney J, Jalal S, Krueger P, Giurleo JT, Ma D, Smith E, Thurston G, Kirshner JR, Crawford A. A PSMA-Targeting CD3 Bispecific Antibody Induces Antitumor Responses that Are Enhanced by 4-1BB Costimulation. Cancer Immunol Res 2020; 8:596-608.
    • Blinatumomab
    • CD19
    • 1 Kantarjian H, Stein A, Gökbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A, Dombret H, Foà R, Bassan R, Arslan Ö, Sanz MA, Bergeron J, Demirkan F, Lech-Maranda E, Rambaldi A, Thomas X, Horst HA, Brüggemann M, Klapper W, Wood BL, Fleishman A, Nagorsen D, Holland C, Zimmerman Z, Topp MS. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med 2017; 376:836-847.
    • Bosutinib
    • ABL1
    • 1B Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim DW, Dyagil I, Glushko N, Milojkovic D, le Coutre P, Garcia-Gutierrez V, Reilly L, Jeynes-Ellis A, Leip E, Bardy-Bouxin N, Hochhaus A, Brümmendorf TH. Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial. J Clin Oncol 2018; 36:231-237.
    • ABL1
    • R1 Nardi V, Azam M, Daley GQ. Mechanisms and implications of imatinib resistance mutations in BCR-ABL. Curr Opin Hematol 2004; 11:35-43.
    • R1 Redaelli S, Piazza R, Rostagno R, Magistroni V, Perini P, Marega M, Gambacorti-Passerini C, Boschelli F. Activity of bosutinib, dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants. J Clin Oncol 2009; 27:469-71.
    • R1 Khoury HJ, Cortes JE, Kantarjian HM, Gambacorti-Passerini C, Baccarani M, Kim DW, Zaritskey A, Countouriotis A, Besson N, Leip E, Kelly V, Brümmendorf TH. Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. Blood 2012; 119:3403-12.
    • NF1, WT1
    • R2 Bigenzahn JW, Collu GM, Kartnig F, Pieraks M, Vladimer GI, Heinz LX, Sedlyarov V, Schischlik F, Fauster A, Rebsamen M, Parapatics K, Blomen VA, Müller AC, Winter GE, Kralovics R, Brummelkamp TR, Mlodzik M, Superti-Furga G. LZTR1 is a regulator of RAS ubiquitination and signaling. Science 2018; 362:1171-1177.
    • ABL1
    • 2 Cortes JE, Kim DW, Kantarjian HM, Brümmendorf TH, Dyagil I, Griskevicius L, Malhotra H, Powell C, Gogat K, Countouriotis AM, Gambacorti-Passerini C. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial. J Clin Oncol 2012; 30:3486-92.
    • 2 Gambacorti-Passerini C, Cortes JE, Lipton JH, Dmoszynska A, Wong RS, Rossiev V, Pavlov D, Gogat Marchant K, Duvillié L, Khattry N, Kantarjian HM, Brümmendorf TH. Safety of bosutinib versus imatinib in the phase 3 BELA trial in newly diagnosed chronic phase chronic myeloid leukemia. Am J Hematol 2014; 89:947-53.
    • 2 Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim DW, Dyagil I, Glushko N, Milojkovic D, le Coutre P, Garcia-Gutierrez V, Reilly L, Jeynes-Ellis A, Leip E, Bardy-Bouxin N, Hochhaus A, Brümmendorf TH. Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial. J Clin Oncol 2018; 36:231-237.
    • ABL1
    • 3 Gambacorti-Passerini C, Brummendorf T, Kantarjian H, Martinelli G, Liu D, Fisher T, Hewes B, Volkert A, Abbas R, Cortes J. Bosutinib (SKI-606) exhibits clinical activity in patients with Philadelphia chromosome positive CML or ALL who failed imatinib. J Clin Oncol 2007; 25(18_suppl): 7006-7006.
    • Brentuximab Vedotin
    • CD30
    • 1 Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, Forero-Torres A, Moskowitz CH, Connors JM, Engert A, Larsen EK, Kennedy DA, Sievers EL, Chen R. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol 2012; 30:2183-9.
    • 1 Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, Matous J, Ramchandren R, Fanale M, Connors JM, Yang Y, Sievers EL, Kennedy DA, Shustov A. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol 2012; 30:2190-6.
    • 1 Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, Chen AI, Stiff P, Gianni AM, Carella A, Osmanov D, Bachanova V, Sweetenham J, Sureda A, Huebner D, Sievers EL, Chi A, Larsen EK, Hunder NN, Walewski J; AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2015; 385:1853-62.
    • 1 Prince HM, Kim YH, Horwitz SM, Dummer R, Scarisbrick J, Quaglino P, Zinzani PL, Wolter P, Sanches JA, Ortiz-Romero PL, Akilov OE, Geskin L, Trotman J, Taylor K, Dalle S, Weichenthal M, Walewski J, Fisher D, Dréno B, Stadler R, Feldman T, Kuzel TM, Wang Y, Palanca-Wessels MC, Zagadailov E, Trepicchio WL, Zhang W, Lin HM, Liu Y, Huebner D, Little M, Whittaker S, Duvic M; ALCANZA study group. Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Lancet 2017; 390:555-566.
    • Brigatinib
    • ALK
    • R2 J. Jean Cui, Evan Rogers, Dayong Zhai, Wei Deng, Jane Ung, Vivian Nguyen, Han Zhang, Xin Zhang, Ana Parra, Maria Barrera, Dong Lee, Brion Murray. TPX-0131: A next generation macrocyclic ALK inhibitor that overcomes ALK resistant mutations refractory to current approved ALK inhibitors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5226.
    • ROS1
    • R2 Davare MA, Vellore NA, Wagner JP, Eide CA, Goodman JR, Drilon A, Deininger MW, O'Hare T, Druker BJ. Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors. Proc Natl Acad Sci U S A 2015; 112:E5381-90.
    • ALK
    • R2 Lin JJ, Riely GJ, Shaw AT. Targeting ALK: Precision Medicine Takes on Drug Resistance. Cancer Discov 2017; 7:137-155.
    • R2 Sabari JK, Santini FC, Schram AM, Bergagnini I, Chen R, Mrad C, Lai WV, Arbour KC, Drilon A. The activity, safety, and evolving role of brigatinib in patients with ALK-rearranged non-small cell lung cancers. Onco Targets Ther 2017; 10:1983-1992. eCollection 2017.
    • R2 Lin JJ, Zhu VW, Schoenfeld AJ, Yeap BY, Saxena A, Ferris LA, Dagogo-Jack I, Farago AF, Taber A, Traynor A, Menon S, Gainor JF, Lennerz JK, Plodkowski AJ, Digumarthy SR, Ou SI, Shaw AT, Riely GJ. Brigatinib in Patients With Alectinib-Refractory ALK-Positive NSCLC. J Thorac Oncol 2018; 13:1530-1538.
    • ROS1
    • R2 Guisier F, Piton N, Salaun M, Thiberville L. ROS1-rearranged NSCLC With Secondary Resistance Mutation: Case Report and Current Perspectives. Clin Lung Cancer 2019; 20:e593-e596.
    • ALK
    • 1 Camidge DR, Kim HR, Ahn MJ, Yang JC, Han JY, Lee JS, Hochmair MJ, Li JY, Chang GC, Lee KH, Gridelli C, Delmonte A, Garcia Campelo R, Kim DW, Bearz A, Griesinger F, Morabito A, Felip E, Califano R, Ghosh S, Spira A, Gettinger SN, Tiseo M, Gupta N, Haney J, Kerstein D, Popat S. Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med 2018; 379:2027-2039.
    • 1 Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, Lee KH, Delmonte A, García Campelo MR, Kim DW, Griesinger F, Felip E, Califano R, Spira A, Gettinger SN, Tiseo M, Lin HM, Gupta N, Hanley MJ, Ni Q, Zhang P, Popat S. Brigatinib Versus Crizotinib in Advanced ALK Inhibitor-Naive ALK-Positive Non-Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial. J Clin Oncol 2020; 38:3592-3603.
    • ALK
    • 3 Lin JJ, Riely GJ, Shaw AT. Targeting ALK: Precision Medicine Takes on Drug Resistance. Cancer Discov 2017; 7:137-155.
    • ROS1
    • 4 Rachel M. Squillace, Rana Anjum, David Miller, Sadanand Vodala, Lauren Moran, Frank Wang, Tim Clackson, Andrew P. Garner, Victor M. Rivera. AP26113 possesses pan-inhibitory activity versus crizotinib-resistant ALK mutants and oncogenic ROS1 fusions. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5655. doi:10.1158/1538-7445.AM2013-5655
    • ALK
    • 4 Bazhenova L, Hodgson JG, Langer CJ, Simon GR, Gettinger SN, Ou SI, Reckamp KL, West HJ, Chiappori A, Koh HA, Molina JR, Shaw AT, Patel JD, Favaro JP, Haney J, Reichmann W, Kerstein D, Rivera VM, Camidge DR. Activity of brigatinib (BRG) in crizotinib (CRZ)-resistant ALK+ NSCLC patients (pts) according to ALK plasma mutation status. J Clin Oncol 2017; 35(15_suppl): 9065-9065.
    • ROS1
    • 4 Hegde A, Hong DS, Behrang A, Ali SM, Juckett L, Meric-Bernstam F, Subbiah V. Activity of Brigatinib in Crizotinib and Ceritinib-Resistant ROS1- Rearranged Non-Small-Cell Lung Cancer. JCO Prec Oncol 2018; 10.1200/PO.18.00267
    • 4 Study of Oral RXDX-101 in Adult Patients With Locally Advanced or Metastatic Cancer Targeting NTRK1, NTRK2, NTRK3, ROS1, or ALK Molecular Alterations. [NCT02097810]
    • 4 Brigatinib in Treating Patients With ALK and ROS1 Gene Alterations and Locally Advanced or Metastatic Solid Cancers [NCT03868423]
    • 4 A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations [NCT04094610]
    • ALK
    • 4 Maxson JE, Davare MA, Luty SB, Eide CA, Chang BH, Loriaux MM, Tognon CE, Bottomly D, Wilmot B, McWeeney SK, Druker BJ, Tyner JW. Therapeutically Targetable ALK Mutations in Leukemia. Cancer Res 2015; 75:2146-50.
    • ROS1
    • 4 Drilon A, Siena S, Ou SI, Patel M, Ahn MJ, Lee J, Bauer TM, Farago AF, Wheler JJ, Liu SV, Doebele R, Giannetta L, Cerea G, Marrapese G, Schirru M, Amatu A, Bencardino K, Palmeri L, Sartore-Bianchi A, Vanzulli A, Cresta S, Damian S, Duca M, Ardini E, Li G, Christiansen J, Kowalski K, Johnson AD, Patel R, Luo D, Chow-Maneval E, Hornby Z, Multani PS, Shaw AT, De Braud FG. Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1). Cancer Discov 2017; 7:400-409.
    • Buparlisib
    • PIK3CA, PIK3R1, PTEN
    • R2 Piha-Paul SA, Taylor MH, Spitz D, Schwartzberg L, Beck JT, Bauer TM, Meric-Bernstam F, Purkayastha D, Karpiak L, Szpakowski S, Braiteh F. Efficacy and safety of buparlisib, a PI3K inhibitor, in patients with malignancies harboring a PI3K pathway activation: a phase 2, open-label, single-arm study. Oncotarget 2019; 10:6526-6535. eCollection 2019 Nov 5.
    • TSC1
    • R2 McPherson V, Reardon B, Bhayankara A, Scott SN, Boyd ME, Garcia-Grossman IR, Regazzi AM, McCoy AS, Kim PH, Al-Ahmadie H, Ostrovnaya I, Roth AJ, Farooki A, Berger MF, Rosenberg JE, Solit DB, Van Allen E, Milowsky MI, Bajorin DF, Iyer G. A phase 2 trial of buparlisib in patients with platinum-resistant metastatic urothelial carcinoma. Cancer 2020 Aug 7. [Epub ahead of print]
    • Buparlisib + Fulvestrant
    • PIK3CA+ESR1+ERBB2
    • 3 Baselga J, Im SA, Iwata H, Cortés J, De Laurentiis M, Jiang Z, Arteaga CL, Jonat W, Clemons M, Ito Y, Awada A, Chia S, Jagiełło-Gruszfeld A, Pistilli B, Tseng LM, Hurvitz S, Masuda N, Takahashi M, Vuylsteke P, Hachemi S, Dharan B, Di Tomaso E, Urban P, Massacesi C, Campone M. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2017; 18:904-916.
    • 3 Di Leo A, Johnston S, Lee KS, Ciruelos E, Lønning PE, Janni W, O'Regan R, Mouret-Reynier MA, Kalev D, Egle D, Csőszi T, Bordonaro R, Decker T, Tjan-Heijnen VCG, Blau S, Schirone A, Weber D, El-Hashimy M, Dharan B, Sellami D, Bachelot T. Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer progressing on or after mTOR inhibition (BELLE-3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2018; 19:87-100.
    • PIK3CA
    • 3 [No authors listed] . Correction to Lancet Oncol 2018; 19: 87-100. Lancet Oncol 2018; 19:e137.
    • Buparlisib + Tamoxifen
    • PIK3CA
    • 4 Welt A, Wiesweg M, Theurer S, Abenhardt W, Groschek M, Müller L, Schröder J, Tewes M, Chiabudini M, Potthoff K, Bankfalvi A, Marschner N, Schuler M, Breitenbücher F. Buparlisib in combination with tamoxifen in pretreated patients with hormone receptor-positive, HER2-negative advanced breast cancer molecularly stratified for PIK3CA mutations and loss of PTEN expression. Cancer Med 2020; 9:4527-4539.
    • bispecific ERBB2/CD3 monoclonal antibody
    • ERBB2
    • 4 A Phase I Study of BTRC4017A in Participants With Locally Advanced or Metastatic HER2-Expressing Cancers [NCT03448042]
    • C
    • CB-103
    • NOTCH1
    • 4 Miranda EL, Stathis A, Hess D, Racca F, Quon D, Rodon J, Gadea OSS, Garcia JMP, Nuciforo P, Vivancos A, Cortes J, Ferrarotto R, Schönborn-Kellenberger O, Vigolo M, Bobadilla M, Beni L, Lehal R, Bauer MP, Vogl FD, Garralda E, Center UoTMAC, Houston , GmbH TC, Heidelberg , R&D G, AG CB, Epalinges , AG SCB, Basel , (UITM) SEDDU, Oncology VdUHaIoO(aM, (HUVH) VdUH, Barcelona , Spain . Phase 1 study of CB-103, a novel first-in-class inhibitor of the CSL-NICD gene transcription factor complex in human cancers. J Clin Oncol 2021; 39(15_suppl): 3020-3020.
    • CCT128930
    • AKT2
    • 4 Yap TA, Walton MI, Hunter LJ, Valenti M, de Haven Brandon A, Eve PD, Ruddle R, Heaton SP, Henley A, Pickard L, Vijayaraghavan G, Caldwell JJ, Thompson NT, Aherne W, Raynaud FI, Eccles SA, Workman P, Collins I, Garrett MD. Preclinical pharmacology, antitumor activity, and development of pharmacodynamic markers for the novel, potent AKT inhibitor CCT128930. Mol Cancer Ther 2011; 10:360-71.
    • 4 Pachl F, Plattner P, Ruprecht B, Médard G, Sewald N, Kuster B. Characterization of a chemical affinity probe targeting Akt kinases. J Proteome Res 2013; 12:3792-800.
    • CH5126766
    • KRAS
    • 4 Guo C, Chénard-Poirier M, Roda D, de Miguel M, Harris SJ, Candilejo IM, Sriskandarajah P, Xu W, Scaranti M, Constantinidou A, King J, Parmar M, Turner AJ, Carreira S, Riisnaes R, Finneran L, Hall E, Ishikawa Y, Nakai K, Tunariu N, Basu B, Kaiser M, Lopez JS, Minchom A, de Bono JS, Banerji U. Intermittent schedules of the oral RAF-MEK inhibitor CH5126766/VS-6766 in patients with RAS/RAF-mutant solid tumours and multiple myeloma: a single-centre, open-label, phase 1 dose-escalation and basket dose-expansion study. Lancet Oncol 2020; 21:1478-1488.
    • CX-5461
    • MYCL
    • 4 Kim DW, Wu N, Kim YC, Cheng PF, Basom R, Kim D, Dunn CT, Lee AY, Kim K, Lee CS, Singh A, Gazdar AF, Harris CR, Eisenman RN, Park KS, MacPherson D. Genetic requirement for Mycl and efficacy of RNA Pol I inhibition in mouse models of small cell lung cancer. Genes Dev 2016; 30:1289-99.
    • MYCN
    • 4 Niemas-Teshiba R, Matsuno R, Wang LL, Tang XX, Chiu B, Zeki J, Coburn J, Ornell K, Naranjo A, Van Ryn C, London WB, Hogarty MD, Gastier-Foster JM, Look AT, Park JR, Maris JM, Cohn SL, Seeger RC, Asgharzadeh S, Ikegaki N, Shimada H. MYC-family protein overexpression and prominent nucleolar formation represent prognostic indicators and potential therapeutic targets for aggressive high-MKI neuroblastomas: a report from the children's oncology group. Oncotarget 2017; 9:6416-6432. eCollection 2018 Jan 19.
    • 4 Hald ØH, Olsen L, Gallo-Oller G, Elfman LHM, Løkke C, Kogner P, Sveinbjörnsson B, Flægstad T, Johnsen JI, Einvik C. Inhibitors of ribosome biogenesis repress the growth of MYCN-amplified neuroblastoma. Oncogene 2019; 38:2800-2813.
    • MYC, MYCN
    • 4 Taylor JS, Zeki J, Ornell K, Coburn J, Shimada H, Ikegaki N, Chiu B. Down-regulation of MYCN protein by CX-5461 leads to neuroblastoma tumor growth suppression. J Pediatr Surg 2019; 54:1192-1197.
    • BRCA1, BRCA2
    • 4 Sanij E, Hannan KM, Xuan J, Yan S, Ahern JE, Trigos AS, Brajanovski N, Son J, Chan KT, Kondrashova O, Lieschke E, Wakefield MJ, Frank D, Ellis S, Cullinane C, Kang J, Poortinga G, Nag P, Deans AJ, Khanna KK, Mileshkin L, McArthur GA, Soong J, Berns EMJJ, Hannan RD, Scott CL, Sheppard KE, Pearson RB. CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer. Nat Commun 2020; 11:2641.
    • CX-5461 + Olaparib
    • BRCA1, BRCA2
    • 4 Sanij E, Hannan KM, Xuan J, Yan S, Ahern JE, Trigos AS, Brajanovski N, Son J, Chan KT, Kondrashova O, Lieschke E, Wakefield MJ, Frank D, Ellis S, Cullinane C, Kang J, Poortinga G, Nag P, Deans AJ, Khanna KK, Mileshkin L, McArthur GA, Soong J, Berns EMJJ, Hannan RD, Scott CL, Sheppard KE, Pearson RB. CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer. Nat Commun 2020; 11:2641.
    • CYP17A1 inhibitor
    • AR, AURKA, MYCN, RB1, TP53
    • R2 Watson PA, Arora VK, Sawyers CL. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nat Rev Cancer 2015; 15:701-11.
    • AR
    • 4 Munoz J, Wheler JJ, Kurzrock R. Androgen receptors beyond prostate cancer: an old marker as a new target. Oncotarget 2015; 6:592-603.
    • 4 Zalcman N, Canello T, Ovadia H, Charbit H, Zelikovitch B, Mordechai A, Fellig Y, Rabani S, Shahar T, Lossos A, Lavon I. Androgen receptor: a potential therapeutic target for glioblastoma. Oncotarget 2018; 9:19980-19993. eCollection 2018 Apr 13.
    • Cabozantinib
    • RET
    • R2 Carlomagno F, Guida T, Anaganti S, Vecchio G, Fusco A, Ryan AJ, Billaud M, Santoro M. Disease associated mutations at valine 804 in the RET receptor tyrosine kinase confer resistance to selective kinase inhibitors. Oncogene 2004; 23:6056-63.
    • KIT
    • R2 Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B, Orf J, You A, Laird AD, Engst S, Lee L, Lesch J, Chou YC, Joly AH. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther 2011; 10:2298-308.
    • ROS1
    • R2 Katayama R, Kobayashi Y, Friboulet L, Lockerman EL, Koike S, Shaw AT, Engelman JA, Fujita N. Cabozantinib overcomes crizotinib resistance in ROS1 fusion-positive cancer. Clin Cancer Res 2015; 21:166-74.
    • R2 Davare MA, Vellore NA, Wagner JP, Eide CA, Goodman JR, Drilon A, Deininger MW, O'Hare T, Druker BJ. Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors. Proc Natl Acad Sci U S A 2015; 112:E5381-90.
    • RET
    • R2 Huang Q, Schneeberger VE, Luetteke N, Jin C, Afzal R, Budzevich MM, Makanji RJ, Martinez GV, Shen T, Zhao L, Fung KM, Haura EB, Coppola D, Wu J. Preclinical Modeling of KIF5B-RET Fusion Lung Adenocarcinoma. Mol Cancer Ther 2016; 15:2521-2529.
    • ROS1
    • R2 Guisier F, Piton N, Salaun M, Thiberville L. ROS1-rearranged NSCLC With Secondary Resistance Mutation: Case Report and Current Perspectives. Clin Lung Cancer 2019; 20:e593-e596.
    • MDM2, RET
    • R2 Subbiah V, Yang D, Velcheti V, Drilon A, Meric-Bernstam F. State-of-the-Art Strategies for Targeting RET-Dependent Cancers. J Clin Oncol 2020; 38:1209-1221.
    • RET
    • 3 Drilon A, Rekhtman N, Arcila M, Wang L, Ni A, Albano M, Van Voorthuysen M, Somwar R, Smith RS, Montecalvo J, Plodkowski A, Ginsberg MS, Riely GJ, Rudin CM, Ladanyi M, Kris MG. Cabozantinib in patients with advanced RET-rearranged non-small-cell lung cancer: an open-label, single-centre, phase 2, single-arm trial. Lancet Oncol 2016; 17:1653-1660.
    • KIT
    • 3 Schöffski P, Mir O, Kasper B, Papai Z, Blay JY, Italiano A, Benson C, Kopeckova K, Ali N, Dileo P, LeCesne A, Menge F, Cousin S, Wardelmann E, Wozniak A, Marreaud S, Litiere S, Zaffaroni F, Nzokirantevye A, Vanden Bempt I, Gelderblom H. Activity and safety of the multi-target tyrosine kinase inhibitor cabozantinib in patients with metastatic gastrointestinal stromal tumour after treatment with imatinib and sunitinib: European Organisation for Research and Treatment of Cancer phase II trial 1317 'CaboGIST'. Eur J Cancer 2020; 134:62-74.
    • KIT
    • ROS1
    • 4 Cabozantinib in Patients With RET Fusion-Positive Advanced Non-Small Cell Lung Cancer and Those With Other Genotypes: ROS1 or NTRK Fusions or Increased MET or AXL Activity [NCT01639508]
    • KIT, MET
    • 4 Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B, Orf J, You A, Laird AD, Engst S, Lee L, Lesch J, Chou YC, Joly AH. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther 2011; 10:2298-308.
    • RET
    • 4 Drilon A, Wang L, Hasanovic A, Suehara Y, Lipson D, Stephens P, Ross J, Miller V, Ginsberg M, Zakowski MF, Kris MG, Ladanyi M, Rizvi N. Response to Cabozantinib in patients with RET fusion-positive lung adenocarcinomas. Cancer Discov 2013; 3:630-5.
    • ROS1
    • 4 Katayama R, Kobayashi Y, Friboulet L, Lockerman EL, Koike S, Shaw AT, Engelman JA, Fujita N. Cabozantinib overcomes crizotinib resistance in ROS1 fusion-positive cancer. Clin Cancer Res 2015; 21:166-74.
    • MET
    • 4 [No authors listed] . Correction: Response to MET Inhibitors in Patients with Stage IV Lung Adenocarcinomas Harboring MET Mutations Causing Exon 14 Skipping. Cancer Discov 2016; 6:330.
    • RET
    • 4 Sherman SI, Clary DO, Elisei R, Schlumberger MJ, Cohen EE, Schöffski P, Wirth LJ, Mangeshkar M, Aftab DT, Brose MS. Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib in patients with progressive, metastatic medullary thyroid cancer. Cancer 2016; 122:3856-3864.
    • MET
    • 4 Klempner SJ, Borghei A, Hakimian B, Ali SM, Ou SI. Intracranial Activity of Cabozantinib in MET Exon 14-Positive NSCLC with Brain Metastases. J Thorac Oncol 2017; 12:152-156.
    • KIT
    • 4 Gebreyohannes YK, Schöffski P, Van Looy T, Wellens J, Vreys L, Cornillie J, Vanleeuw U, Aftab DT, Debiec-Rychter M, Sciot R, Wozniak A. Cabozantinib Is Active against Human Gastrointestinal Stromal Tumor Xenografts Carrying Different KIT Mutations. Mol Cancer Ther 2016; 15:2845-2852.
    • MET
    • 4 Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Huang Y, Carbone DP, Gerstner GJ, Lerner RE, Rubin JL, Owonikoko TK, Stella PJ, Steen PD, Khalid AA, Ramalingam SS; ECOG-ACRIN 1512 Investigators. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol 2016; 17:1661-1671.
    • RET
    • 4 Schlumberger M, Elisei R, Müller S, Schöffski P, Brose M, Shah M, Licitra L, Krajewska J, Kreissl MC, Niederle B, Cohen EEW, Wirth L, Ali H, Clary DO, Yaron Y, Mangeshkar M, Ball D, Nelkin B, Sherman S. Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma. Ann Oncol 2017; 28:2813-2819.
    • 4 Wang Y, Xu Y, Wang X, Sun C, Guo Y, Shao G, Yang Z, Qiu S, Ma K. RET fusion in advanced non-small-cell lung cancer and response to cabozantinib: A case report. Medicine (Baltimore) 2019; 98:e14120.
    • MET
    • 4 Wang SXY, Zhang BM, Wakelee HA, Koontz MZ, Pan M, Diehn M, Kunder CA, Neal JW. Case series of MET exon 14 skipping mutation-positive non-small-cell lung cancers with response to crizotinib and cabozantinib. Anticancer Drugs 2019; 30:537-541.
    • ROS1
    • 4 Guisier F, Piton N, Salaun M, Thiberville L. ROS1-rearranged NSCLC With Secondary Resistance Mutation: Case Report and Current Perspectives. Clin Lung Cancer 2019; 20:e593-e596.
    • 4 Wang G, Gao J, Lv J, Chen X, Wu J, Wang R, Jiang J. Effective Treatment with Cabozantinib in an Advanced Non-Small-Cell Lung Cancer Patient Harboring a CD74-ROS1 Fusion: A Case Report. Onco Targets Ther 2020; 13:1171-1177. eCollection 2020.
    • MET
    • 4 Parsons BM, Meier DR, Richmond CS, Gurda GT, Lofgren KA, Burkard ME, Deming DA, Kenny PA. Acquisition of Cabozantinib-Sensitive MET D1228N Mutation During Progression on Crizotinib in MET-Amplified Triple-Negative Breast Cancer. Clin Breast Cancer 2020; 20:e433-e438.
    • Cabozantinib + Nivolumab
    • SETD2
    • R2 Lee CH, Voss MH, Carlo MI, Chen YB, Zucker M, Knezevic A, Lefkowitz RA, Shapnik N, Dadoun C, Reznik E, Shah NJ, Owens CN, McHugh DJ, Aggen DH, Laccetti AL, Kotecha R, Feldman DR, Motzer RJ. Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates. J Clin Oncol 2022 Mar 17:JCO2101944. [Epub ahead of print]
    • FH, NF2
    • 4 Lee CH, Voss MH, Carlo MI, Chen YB, Zucker M, Knezevic A, Lefkowitz RA, Shapnik N, Dadoun C, Reznik E, Shah NJ, Owens CN, McHugh DJ, Aggen DH, Laccetti AL, Kotecha R, Feldman DR, Motzer RJ. Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates. J Clin Oncol 2022 Mar 17:JCO2101944. [Epub ahead of print]
    • Camrelizumab
    • CD274
    • 3 Huang J, Xu J, Chen Y, Zhuang W, Zhang Y, Chen Z, Chen J, Zhang H, Niu Z, Fan Q, Lin L, Gu K, Liu Y, Ba Y, Miao Z, Jiang X, Zeng M, Chen J, Fu Z, Gan L, Wang J, Zhan X, Liu T, Li Z, Shen L, Shu Y, Zhang T, Yang Q, Zou J; ESCORT Study Group. Camrelizumab versus investigator's choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study. Lancet Oncol 2020; 21:832-842.
    • Capecitabine + Bevacizumab
    • Consensus molecular subtype
    • 4 Mooi JK, Wirapati P, Asher R, Lee CK, Savas P, Price TJ, Townsend A, Hardingham J, Buchanan D, Williams D, Tejpar S, Mariadason JM, Tebbutt NC. The prognostic impact of consensus molecular subtypes (CMS) and its predictive effects for bevacizumab benefit in metastatic colorectal cancer: molecular analysis of the AGITG MAX clinical trial. Ann Oncol 2018; 29:2240-2246.
    • Capecitabine + Temozolomide
    • MGMT
    • 4 . . [DOI:]
    • Capecitabine + Trastuzumab + Tucatinib
    • ERBB2
    • 1B Lin NU, Murthy RK, Anders CK, Borges VF, Hurvitz SA, Loi S, Abramson VG, Bedard PL, Oliveira M, Zelnak AB, DiGiovanna M, Bachelot T, Chien AJ, O'Regan R, Wardley AM, Müller V, Carey LA, McGoldrick SM, An G, Winer EP, MA UMCHGUoNCCHNSCHSWSGIBWDCIHMSB. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB). J Clin Oncol 2020; 38(15_suppl): 1005-1005.
    • 1B Murthy R, Borges VF, Conlin A, Chaves J, Chamberlain M, Gray T, Vo A, Hamilton E. Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study. Lancet Oncol 2018; 19:880-888.
    • 1B Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, Lin NU, Borges V, Abramson V, Anders C, Bedard PL, Oliveira M, Jakobsen E, Bachelot T, Shachar SS, Müller V, Braga S, Duhoux FP, Greil R, Cameron D, Carey LA, Curigliano G, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Palanca-Wessels MC, Walker L, Feng W, Winer EP. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med 2020; 382:597-609.
    • 1B Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O'Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. J Clin Oncol 2020; 38:2610-2619.
    • 1B Curigliano G, Mueller V, Borges V, Hamilton E, Hurvitz S, Loi S, Murthy R, Okines A, Paplomata E, Cameron D, Carey LA, Gelmon K, Hortobagyi GN, Krop I, Loibl S, Pegram M, Slamon D, Ramos J, Feng W, Winer E. Tucatinib vs Placebo Added to Trastuzumab and Capecitabine for Patients with Pretreated HER2+ Metastatic Breast Cancer with and without Brain Metastases (HER2CLIMB): Final Overall Survival Analysis. Ann Oncol 2021 Dec 22. pii: S0923-7534(21)04879-1. [Epub ahead of print]
    • Capivasertib
    • AKT1
    • 3 Kalinsky K, Hong F, McCourt CK, Sachdev JC, Mitchell EP, Zwiebel JA, Doyle LA, McShane LM, Li S, Gray RJ, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Conley BA, O'Dwyer PJ, Harris LN, Arteaga CL, Chen AP, Flaherty KT. Effect of Capivasertib in Patients With an AKT1 E17K-Mutated Tumor: NCI-MATCH Subprotocol EAY131-Y Nonrandomized Trial. JAMA Oncol 2020 Dec 30. [Epub ahead of print]
    • AKT1
    • 4 Hyman DM, Smyth LM, Donoghue MTA, Westin SN, Bedard PL, Dean EJ, Bando H, El-Khoueiry AB, Pérez-Fidalgo JA, Mita A, Schellens JHM, Chang MT, Reichel JB, Bouvier N, Selcuklu SD, Soumerai TE, Torrisi J, Erinjeri JP, Ambrose H, Barrett JC, Dougherty B, Foxley A, Lindemann JPO, McEwen R, Pass M, Schiavon G, Berger MF, Chandarlapaty S, Solit DB, Banerji U, Baselga J, Taylor BS. AKT Inhibition in Solid Tumors With AKT1 Mutations. J Clin Oncol 2017; 35:2251-2259.
    • 4 Smyth LM, Tamura K, Oliveira M, Ciruelos EM, Mayer IA, Sablin MP, Biganzoli L, Ambrose HJ, Ashton J, Barnicle A, Cashell DD, Corcoran C, de Bruin EC, Foxley A, Hauser J, Lindemann JPO, Maudsley R, McEwen R, Moschetta M, Pass M, Rowlands V, Schiavon G, Banerji U, Scaltriti M, Taylor BS, Chandarlapaty S, Baselga J, Hyman DM. Capivasertib, an AKT Kinase Inhibitor, as Monotherapy or in Combination with Fulvestrant in Patients with AKT1 E17K-Mutant, ER-Positive Metastatic Breast Cancer. Clin Cancer Res 2020; 26:3947-3957.
    • Capivasertib + Fulvestrant
    • AKT1, PIK3CA, PTEN
    • 3 Jones RH, Casbard AC, Carucci M, Ingarfield-Herbert K, Butler R, Morgan S, Meissner M, Bale CJ, Bezecny P, Moon S, Twelves C, Venkitaraman R, Waters S, Bruin ED, Schiavon G, Foxley A, Howell SJ, Manchester , Kingdom U. Fulvestrant plus capivasertib versus fulvestrant plus placebo after relapse or progression on an aromatase inhibitor in metastatic, estrogen receptor–positive breast cancer (FAKTION): Overall survival and updated progression-free survival data with enhanced biomarker analysis. J Clin Oncol 2022; 40(16_suppl): 1005-1005.
    • 3 Howell SJ, Casbard A, Carucci M, Ingarfield K, Butler R, Morgan S, Meissner M, Bale C, Bezecny P, Moon S, Twelves C, Venkitaraman R, Waters S, de Bruin EC, Schiavon G, Foxley A, Jones RH. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial. Lancet Oncol 2022 Jun 1. pii: S1470-2045(22)00284-4. [Epub ahead of print]
    • AKT1
    • 4 Smyth LM, Tamura K, Oliveira M, Ciruelos EM, Mayer IA, Sablin MP, Biganzoli L, Ambrose HJ, Ashton J, Barnicle A, Cashell DD, Corcoran C, de Bruin EC, Foxley A, Hauser J, Lindemann JPO, Maudsley R, McEwen R, Moschetta M, Pass M, Rowlands V, Schiavon G, Banerji U, Scaltriti M, Taylor BS, Chandarlapaty S, Baselga J, Hyman DM. Capivasertib, an AKT Kinase Inhibitor, as Monotherapy or in Combination with Fulvestrant in Patients with AKT1 E17K-Mutant, ER-Positive Metastatic Breast Cancer. Clin Cancer Res 2020; 26:3947-3957.
    • Capivasertib + Paclitaxel
    • ESR1+PIK3CA
    • R2 Turner NC, Alarcón E, Armstrong AC, Philco M, López Chuken YA, Sablin MP, Tamura K, Gómez Villanueva A, Pérez-Fidalgo JA, Cheung SYA, Corcoran C, Cullberg M, Davies BR, de Bruin EC, Foxley A, Lindemann JPO, Maudsley R, Moschetta M, Outhwaite E, Pass M, Rugman P, Schiavon G, Oliveira M. BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population. Ann Oncol 2019; 30:774-780.
    • AKT1, PIK3CA, PTEN
    • 3 Schmid P, Abraham J, Chan S, Wheatley D, Brunt AM, Nemsadze G, Baird RD, Park YH, Hall PS, Perren T, Stein RC, Mangel L, Ferrero JM, Phillips M, Conibear J, Cortes J, Foxley A, de Bruin EC, McEwen R, Stetson D, Dougherty B, Sarker SJ, Prendergast A, McLaughlin-Callan M, Burgess M, Lawrence C, Cartwright H, Mousa K, Turner NC. Capivasertib Plus Paclitaxel Versus Placebo Plus Paclitaxel As First-Line Therapy for Metastatic Triple-Negative Breast Cancer: The PAKT Trial. J Clin Oncol 2020; 38:423-433.
    • Capmatinib
    • EGFR, ERBB3, MET
    • R2 Recondo G, Bahcall M, Spurr LF, Che J, Ricciuti B, Leonardi GC, Lo YC, Li YY, Lamberti G, Nguyen T, Milan MSD, Venkatraman D, Umeton R, Paweletz CP, Albayrak A, Cherniack AD, Price KS, Fairclough SR, Nishino M, Sholl LM, Oxnard GR, Jänne PA, Awad MM. Molecular Mechanisms of Acquired Resistance to MET Tyrosine Kinase Inhibitors in Patients with MET Exon 14-Mutant NSCLC. Clin Cancer Res 2020; 26:2615-2625.
    • MET
    • 2 Wolf J, Seto T, Han J, Reguart N, Garon EB, Groen HJ, Tan DS, Hida T, Jonge MJD, Orlov SV, Smit EF, Souquet PJ, Vansteenkiste JF, Giovannini M, Mouhaer SL, Robeva A, Waldron-Lynch M, Heist RS, MA GHCCB. Capmatinib (INC280) in METΔex14-mutated advanced non-small cell lung cancer (NSCLC): Efficacy data from the phase II GEOMETRY mono-1 study. J Clin Oncol 2019; 37(15_suppl): 9004-9004.
    • 2 Wolf J, Seto T, Han JY, Reguart N, Garon EB, Groen HJM, Tan DSW, Hida T, de Jonge M, Orlov SV, Smit EF, Souquet PJ, Vansteenkiste J, Hochmair M, Felip E, Nishio M, Thomas M, Ohashi K, Toyozawa R, Overbeck TR, de Marinis F, Kim TM, Laack E, Robeva A, Le Mouhaer S, Waldron-Lynch M, Sankaran B, Balbin OA, Cui X, Giovannini M, Akimov M, Heist RS; GEOMETRY mono-1 Investigators. Capmatinib in MET Exon 14-Mutated or MET-Amplified Non-Small-Cell Lung Cancer. N Engl J Med 2020; 383:944-957.
    • MET
    • 3 Wolf J, Seto T, Han J, Reguart N, Garon EB, Groen HJ, Tan DS, Hida T, Jonge MJD, Orlov SV, Smit EF, Souquet PJ, Vansteenkiste JF, Giovannini M, Mouhaer SL, Robeva A, Waldron-Lynch M, Heist RS, MA GHCCB. Capmatinib (INC280) in METΔex14-mutated advanced non-small cell lung cancer (NSCLC): Efficacy data from the phase II GEOMETRY mono-1 study. J Clin Oncol 2019; 37(15_suppl): 9004-9004.
    • 3 Wolf J, Overbeck TR, Han J, Hochmair M, Marinis Fd, Ohashi K, Smit EF, Power D, Garon EB, Groen HJ, Tan DS, Waldron-Lynch M, Mouhaer SL, Nwana N, Giovannini M, Heist RS. Capmatinib in patients with high-level MET-amplified advanced non–small cell lung cancer (NSCLC): results from the phase 2 GEOMETRY mono-1 study. J Clin Oncol 2020; 38(15_suppl): 9509-9509.
    • 3 Wolf J, Seto T, Han JY, Reguart N, Garon EB, Groen HJM, Tan DSW, Hida T, de Jonge M, Orlov SV, Smit EF, Souquet PJ, Vansteenkiste J, Hochmair M, Felip E, Nishio M, Thomas M, Ohashi K, Toyozawa R, Overbeck TR, de Marinis F, Kim TM, Laack E, Robeva A, Le Mouhaer S, Waldron-Lynch M, Sankaran B, Balbin OA, Cui X, Giovannini M, Akimov M, Heist RS; GEOMETRY mono-1 Investigators. Capmatinib in MET Exon 14-Mutated or MET-Amplified Non-Small-Cell Lung Cancer. N Engl J Med 2020; 383:944-957.
    • NF1+MET
    • 4 . [PMID:]
    • Capmatinib + Gefitinib
    • EGFR+MET
    • 3 Wu YL, Zhang L, Kim DW, Liu X, Lee DH, Yang JC, Ahn MJ, Vansteenkiste JF, Su WC, Felip E, Chia V, Glaser S, Pultar P, Zhao S, Peng B, Akimov M, Tan DSW. Phase Ib/II Study of Capmatinib (INC280) Plus Gefitinib After Failure of Epidermal Growth Factor Receptor (EGFR) Inhibitor Therapy in Patients With EGFR-Mutated, MET Factor-Dysregulated Non-Small-Cell Lung Cancer. J Clin Oncol 2018; 36:3101-3109.
    • Capmatinib + Trametinib
    • NF1+MET
    • 4 . [PMID:]
    • Carboplatin
    • EMSY
    • 4 Hollis RL, Churchman M, Michie CO, Rye T, Knight L, McCavigan A, Perren T, Williams ARW, McCluggage WG, Kaplan RS, Jayson GC, Oza A, Harkin DP, Herrington CS, Kennedy R, Gourley C. High EMSY expression defines a BRCA-like subgroup of high-grade serous ovarian carcinoma with prolonged survival and hypersensitivity to platinum. Cancer 2019; 125:2772-2781.
    • Carboplatin + Paclitaxel + Bevacizumab
    • TP53
    • 4 Thiel KW, Devor EJ, Filiaci VL, Mutch D, Moxley K, Alvarez Secord A, Tewari KS, McDonald ME, Mathews C, Cosgrove C, Dewdney S, Aghajanian C, Samuelson MI, Lankes HA, Soslow RA, Leslie KK. TP53 Sequencing and p53 Immunohistochemistry Predict Outcomes When Bevacizumab Is Added to Frontline Chemotherapy in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study. J Clin Oncol 2022 Jun 3:JCO2102506. [Epub ahead of print]
    • Carboplatin + Paclitaxel + Trastuzumab
    • ERBB2
    • 3 Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers SK, Secord AA, Havrilesky L, O'Malley DM, Backes F, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi KS, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu. J Clin Oncol 2018; 36:2044-2051.
    • 3 Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers S, Secord AA, Havrilesky L, O'Malley DM, Backes FJ, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi K, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin-Paclitaxel Compared with Carboplatin-Paclitaxel-Trastuzumab in Advanced (Stage III-IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis. Clin Cancer Res 2020; 26:3928-3935.
    • Carboxyamidotriazole Orotate + Temozolomide
    • EGFR
    • 4 Omuro A, Beal K, McNeill K, Young RJ, Thomas A, Lin X, Terziev R, Kaley TJ, DeAngelis LM, Daras M, Gavrilovic IT, Mellinghoff I, Diamond EL, McKeown A, Manne M, Caterfino A, Patel K, Bavisotto L, Gorman G, Lamson M, Gutin P, Tabar V, Chakravarty D, Chan TA, Brennan CW, Garrett-Mayer E, Karmali RA, Pentsova E. Multicenter Phase IB Trial of Carboxyamidotriazole Orotate and Temozolomide for Recurrent and Newly Diagnosed Glioblastoma and Other Anaplastic Gliomas. J Clin Oncol 2018; 36:1702-1709.
    • Cemiplimab
    • CD274
    • 2 Sezer A, Kilickap S, Gümüş M, Bondarenko I, Özgüroğlu M, Gogishvili M, Turk H, Çiçin , Bentsion D, Gladkov O, Clingan P, Sriuranpong V, Rizvi N, Li S, Lee S, Gullo G, Lowy I, Rietschel P. LBA52 EMPOWER-Lung 1: Phase III first-line (1L) cemiplimab monotherapy vs platinum-doublet chemotherapy (chemo) in advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%. Ann Oncol 2020; 31 (4): S1182. 10.1016/j.annonc.2020.08.2285
    • 2 Sezer A, Kilickap S, Gümüş M, Bondarenko I, Özgüroğlu M, Gogishvili M, Turk HM, Cicin I, Bentsion D, Gladkov O, Clingan P, Sriuranpong V, Rizvi N, Gao B, Li S, Lee S, McGuire K, Chen CI, Makharadze T, Paydas S, Nechaeva M, Seebach F, Weinreich DM, Yancopoulos GD, Gullo G, Lowy I, Rietschel P. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet 2021; 397:592-604.
    • Ceralasertib
    • ARID1A
    • 3 Aggarwal R, Umetsu S, Dhawan M, Grabowsky J, Carnevale J, Howell M, Wilch L, Chapman J, Alvarez E, Calabrese S, Smith S, Shah N, Dean E, Munster P, Collisson E. 512O Interim results from a phase II study of the ATR inhibitor ceralasertib in ARID1A-deficient and ARID1A-intact advanced solid tumor malignancies. Ann Oncol 2021; 32 (5): S583. 10.1016/j.annonc.2021.08.1034
    • ATM, ATR
    • 4 Michael Y. Choi, Jessie-Farah Fecteau, Jeff Brown, Alan Lau, Thomas J. Kipps. Induction of proliferation sensitizes chronic lymphocytic leukemia cells to apoptosis mediated by the ATR inhibitor AZD6738. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5485. doi:10.1158/1538-7445.AM2014-5485
    • PBRM1
    • 4 Chabanon RM, Morel D, Eychenne T, Colmet-Daage L, Bajrami I, Dorvault N, Garrido M, Meisenberg C, Lamb A, Ngo C, Hopkins SR, Roumeliotis TI, Jouny S, Hénon C, Kawai-Kawachi A, Astier C, Konde A, Del Nery E, Massard C, Pettitt SJ, Margueron R, Choudhary JS, Almouzni G, Soria JC, Deutsch E, Downs JA, Lord CJ, Postel-Vinay S. PBRM1 Deficiency Confers Synthetic Lethality to DNA Repair Inhibitors in Cancer. Cancer Res 2021 Apr 22. [Epub ahead of print]
    • Ceralasertib + Adavosertib
    • CCNE1
    • 4 Xu H, George E, Kinose Y, Kim H, Shah JB, Peake JD, Ferman B, Medvedev S, Murtha T, Barger CJ, Devins KM, D'Andrea K, Wubbenhorst B, Schwartz LE, Hwang WT, Mills GB, Nathanson KL, Karpf AR, Drapkin R, Brown EJ, Simpkins F. CCNE1 copy number is a biomarker for response to combination WEE1-ATR inhibition in ovarian and endometrial cancer models. Cell Rep Med 2021; 2:100394. eCollection 2021 Sep 21.
    • Ceralasertib + Olaparib
    • ARID1A
    • R2 Aggarwal R, Umetsu S, Dhawan M, Grabowsky J, Carnevale J, Howell M, Wilch L, Chapman J, Alvarez E, Calabrese S, Smith S, Shah N, Dean E, Munster P, Collisson E. 512O Interim results from a phase II study of the ATR inhibitor ceralasertib in ARID1A-deficient and ARID1A-intact advanced solid tumor malignancies. Ann Oncol 2021; 32 (5): S583. 10.1016/j.annonc.2021.08.1034
    • BRCA1, BRCA2, Homologous Recombination Deficiency Score
    • 3 Wethington SL, Shah PD, Martin LP, Tanyi JL, Latif NA, Morgan MA, Torigian DA, Pagan C, Rodriguez D, Domchek SM, Drapkin R, Shih I, Smith S, Dean E, Armstrong DK, Gaillard S, Simpkins F. Combination of PARP and ATR inhibitors (olaparib and ceralasertib) shows clinical activity in acquired PARP inhibitor-resistant recurrent ovarian cancer. J Clin Oncol 2021; 39(15_suppl): 5516-5516.
    • ATM
    • 4 Mahdi H, Hafez N, Doroshow D, Sohal D, Keedy V, Do KT, LoRusso P, Jürgensmeier J, Avedissian M, Sklar J, Glover C, Felicetti B, Dean E, Mortimer P, Shapiro GI, Eder JP. Ceralasertib-Mediated ATR Inhibition Combined With Olaparib in Advanced Cancers Harboring DNA Damage Response and Repair Alterations (Olaparib Combinations). JCO Precis Oncol 2021; 5. pii: PO.20.00439. eCollection 2021.
    • Ceritinib
    • ALK
    • R2 J. Jean Cui, Evan Rogers, Dayong Zhai, Wei Deng, Jane Ung, Vivian Nguyen, Han Zhang, Xin Zhang, Ana Parra, Maria Barrera, Dong Lee, Brion Murray. TPX-0131: A next generation macrocyclic ALK inhibitor that overcomes ALK resistant mutations refractory to current approved ALK inhibitors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5226.
    • ROS1
    • R2 Davare MA, Vellore NA, Wagner JP, Eide CA, Goodman JR, Drilon A, Deininger MW, O'Hare T, Druker BJ. Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors. Proc Natl Acad Sci U S A 2015; 112:E5381-90.
    • ALK
    • R2 Hatcher JM, Bahcall M, Choi HG, Gao Y, Sim T, George R, Jänne PA, Gray NS. Discovery of Inhibitors That Overcome the G1202R Anaplastic Lymphoma Kinase Resistance Mutation. J Med Chem 2015; 58:9296-9308.
    • R2 Holla VR, Elamin YY, Bailey AM, Johnson AM, Litzenburger BC, Khotskaya YB, Sanchez NS, Zeng J, Shufean MA, Shaw KR, Mendelsohn J, Mills GB, Meric-Bernstam F, Simon GR. ALK: a tyrosine kinase target for cancer therapy. Cold Spring Harb Mol Case Stud 2017; 3:a001115.
    • R2 Lin JJ, Riely GJ, Shaw AT. Targeting ALK: Precision Medicine Takes on Drug Resistance. Cancer Discov 2017; 7:137-155.
    • ROS1
    • R2 Guisier F, Piton N, Salaun M, Thiberville L. ROS1-rearranged NSCLC With Secondary Resistance Mutation: Case Report and Current Perspectives. Clin Lung Cancer 2019; 20:e593-e596.
    • ALK
    • 1 Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY, Goldwasser M, Boral AL, Engelman JA. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med 2014; 370:1189-97.
    • 1 Soria JC, Tan DSW, Chiari R, Wu YL, Paz-Ares L, Wolf J, Geater SL, Orlov S, Cortinovis D, Yu CJ, Hochmair M, Cortot AB, Tsai CM, Moro-Sibilot D, Campelo RG, McCulloch T, Sen P, Dugan M, Pantano S, Branle F, Massacesi C, de Castro G Jr. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet 2017; 389:917-929.
    • 1 Shaw AT, Kim TM, Crinò L, Gridelli C, Kiura K, Liu G, Novello S, Bearz A, Gautschi O, Mok T, Nishio M, Scagliotti G, Spigel DR, Deudon S, Zheng C, Pantano S, Urban P, Massacesi C, Viraswami-Appanna K, Felip E. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2017; 18:874-886.
    • ALK
    • 3 Lin JJ, Riely GJ, Shaw AT. Targeting ALK: Precision Medicine Takes on Drug Resistance. Cancer Discov 2017; 7:137-155.
    • ROS1
    • 3 Lim SM, Kim HR, Lee JS, Lee KH, Lee YG, Min YJ, Cho EK, Lee SS, Kim BS, Choi MY, Shim HS, Chung JH, La Choi Y, Lee MJ, Kim M, Kim JH, Ali SM, Ahn MJ, Cho BC. Open-Label, Multicenter, Phase II Study of Ceritinib in Patients With Non-Small-Cell Lung Cancer Harboring ROS1 Rearrangement. J Clin Oncol 2017; 35:2613-2618.
    • ALK
    • 4 Schulte JH, Moreno L, Ziegler DS, Marshall LV, Zwaan CM, Irwin M, Casanova M, Sabado C, Wulff B, Stegert M, Wang L, Hurtado FK, Branle F, Fischer M, Geoerger B. Final analysis of phase I study of ceritinib in pediatric patients with malignancies harboring activated anaplastic lymphoma kinase (ALK). J Clin Oncol 2020; 38(15_suppl): 10505-10505.
    • 4 Awad MM, Shaw AT. ALK inhibitors in non-small cell lung cancer: crizotinib and beyond. Clin Adv Hematol Oncol 2014; 12:429-39
    • 4 Maxson JE, Davare MA, Luty SB, Eide CA, Chang BH, Loriaux MM, Tognon CE, Bottomly D, Wilmot B, McWeeney SK, Druker BJ, Tyner JW. Therapeutically Targetable ALK Mutations in Leukemia. Cancer Res 2015; 75:2146-50.
    • 4 Davare MA, Vellore NA, Wagner JP, Eide CA, Goodman JR, Drilon A, Deininger MW, O'Hare T, Druker BJ. Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors. Proc Natl Acad Sci U S A 2015; 112:E5381-90.
    • 4 Menichincheri M, Ardini E, Magnaghi P, Avanzi N, Banfi P, Bossi R, Buffa L, Canevari G, Ceriani L, Colombo M, Corti L, Donati D, Fasolini M, Felder E, Fiorelli C, Fiorentini F, Galvani A, Isacchi A, Borgia AL, Marchionni C, Nesi M, Orrenius C, Panzeri A, Pesenti E, Rusconi L, Saccardo MB, Vanotti E, Perrone E, Orsini P. Discovery of Entrectinib: A New 3-Aminoindazole As a Potent Anaplastic Lymphoma Kinase (ALK), c-ros Oncogene 1 Kinase (ROS1), and Pan-Tropomyosin Receptor Kinases (Pan-TRKs) inhibitor. J Med Chem 2016; 59:3392-408.
    • 4 Ono A, Murakami H, Serizawa M, Wakuda K, Kenmotsu H, Naito T, Taira T, Koh Y, Ohde Y, Nakajima T, Endo M, Takahashi T. Drastic initial response and subsequent response to two ALK inhibitors in a patient with a highly aggressive ALK-rearranged inflammatory myofibroblastic tumor arising in the pleural cavity. Lung Cancer 2016; 99:151-4.
    • 4 Saiki M, Ohyanagi F, Ariyasu R, Koyama J, Sonoda T, Nishikawa S, Kitazono S, Yanagitani N, Horiike A, Ninomiya H, Ishikawa Y, Nishio M. Dramatic response to alectinib in inflammatory myofibroblastic tumor with anaplastic lymphoma kinase fusion gene. Jpn J Clin Oncol 2017; 47:1189-1192.
    • 4 Honda K, Kadowaki S, Kato K, Hanai N, Hasegawa Y, Yatabe Y, Muro K. Durable response to the ALK inhibitor alectinib in inflammatory myofibroblastic tumor of the head and neck with a novel SQSTM1-ALK fusion: a case report. Invest New Drugs 2019; 37:791-795.
    • 4 Li Y, Chen X, Qu Y, Fan JM, Li Y, Peng H, Zheng Y, Zhang Y, Zhang HB. Partial Response to Ceritinib in a Patient With Abdominal Inflammatory Myofibroblastic Tumor Carrying a TFG-ROS1 Fusion. J Natl Compr Canc Netw 2019; 17:1459-1462.
    • IRS2
    • 4 Lee MS, Jung K, Song JY, Sung MJ, Ahn SB, Lee B, Oh DY, Choi YL. IRS2 Amplification as a Predictive Biomarker in Response to Ceritinib in Small Cell Lung Cancer. Mol Ther Oncolytics 2020; 16:188-196. eCollection 2020 Mar 27.
    • Cetuximab
    • KRAS, NRAS
    • R1 Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008; 359:1757-65.
    • BRAF
    • R1 De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F, Rougier P, Vincenzi B, Santini D, Tonini G, Cappuzzo F, Frattini M, Molinari F, Saletti P, De Dosso S, Martini M, Bardelli A, Siena S, Sartore-Bianchi A, Tabernero J, Macarulla T, Di Fiore F, Gangloff AO, Ciardiello F, Pfeiffer P, Qvortrup C, Hansen TP, Van Cutsem E, Piessevaux H, Lambrechts D, Delorenzi M, Tejpar S. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol 2010; 11:753-62.
    • KRAS, NRAS
    • R1 Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 2013; 369:1023-34.
    • ERBB2
    • R2 Raghav K, Loree JM, Morris JS, Overman MJ, Yu R, Meric-Bernstam F, Menter D, Korphaisarn K, Kee B, Muranyi A, Singh S, Routbort M, Chen K, Shaw KR, Katkhuda R, Shanmugam K, Maru D, Fakih M, Kopetz S. Validation of HER2 Amplification as a Predictive Biomarker for Anti-Epidermal Growth Factor Receptor Antibody Therapy in Metastatic Colorectal Cancer. JCO Prec Oncol 2018; - published online January 22, 2019
    • EGFR
    • R2 Neyns B, Sadones J, Joosens E, Bouttens F, Verbeke L, Baurain JF, D'Hondt L, Strauven T, Chaskis C, In't Veld P, Michotte A, De Greve J. Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma. Ann Oncol 2009; 20:1596-1603.
    • R2 Montagut C, Dalmases A, Bellosillo B, Crespo M, Pairet S, Iglesias M, Salido M, Gallen M, Marsters S, Tsai SP, Minoche A, Seshagiri S, Serrano S, Himmelbauer H, Bellmunt J, Rovira A, Settleman J, Bosch F, Albanell J. Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer. Nat Med 2012; 18:221-3.
    • KRAS
    • R2 Valtorta E, Misale S, Sartore-Bianchi A, Nagtegaal ID, Paraf F, Lauricella C, Dimartino V, Hobor S, Jacobs B, Ercolani C, Lamba S, Scala E, Veronese S, Laurent-Puig P, Siena S, Tejpar S, Mottolese M, Punt CJ, Gambacorta M, Bardelli A, Di Nicolantonio F. KRAS gene amplification in colorectal cancer and impact on response to EGFR-targeted therapy. Int J Cancer 2013; 133:1259-65.
    • EGFR
    • R2 Arena S, Bellosillo B, Siravegna G, Martínez A, Cañadas I, Lazzari L, Ferruz N, Russo M, Misale S, González I, Iglesias M, Gavilan E, Corti G, Hobor S, Crisafulli G, Salido M, Sánchez J, Dalmases A, Bellmunt J, De Fabritiis G, Rovira A, Di Nicolantonio F, Albanell J, Bardelli A, Montagut C. Emergence of Multiple EGFR Extracellular Mutations during Cetuximab Treatment in Colorectal Cancer. Clin Cancer Res 2015; 21:2157-66.
    • HRAS
    • R2 Boidot R, Chevrier S, Julie V, Ladoire S, Ghiringhelli F. HRAS G13D, a new mutation implicated in the resistance to anti-EGFR therapies in colorectal cancer, a case report. Int J Colorectal Dis 2016; 31:1245-6.
    • KRAS
    • R2 Segelov E, Thavaneswaran S, Waring PM, Desai J, Robledo KP, Gebski VJ, Elez E, Nott LM, Karapetis CS, Lunke S, Chantrill LA, Pavlakis N, Khasraw M, Underhill C, Ciardiello F, Jefford M, Wasan H, Haydon A, Price TJ, van Hazel G, Wilson K, Simes J, Shapiro JD. Response to Cetuximab With or Without Irinotecan in Patients With Refractory Metastatic Colorectal Cancer Harboring the KRAS G13D Mutation: Australasian Gastro-Intestinal Trials Group ICECREAM Study. J Clin Oncol 2016; 34:2258-64.
    • ERBB4
    • R2 Nakamura Y, Togashi Y, Nakahara H, Tomida S, Banno E, Terashima M, Hayashi H, de Velasco MA, Sakai K, Fujita Y, Okegawa T, Nutahara K, Hamada S, Nishio K. Afatinib against Esophageal or Head-and-Neck Squamous Cell Carcinoma: Significance of Activating Oncogenic HER4 Mutations in HNSCC. Mol Cancer Ther 2016; 15:1988-97.
    • EGFR
    • R2 Van Emburgh BO, Arena S, Siravegna G, Lazzari L, Crisafulli G, Corti G, Mussolin B, Baldi F, Buscarino M, Bartolini A, Valtorta E, Vidal J, Bellosillo B, Germano G, Pietrantonio F, Ponzetti A, Albanell J, Siena S, Sartore-Bianchi A, Di Nicolantonio F, Montagut C, Bardelli A. Acquired RAS or EGFR mutations and duration of response to EGFR blockade in colorectal cancer. Nat Commun 2016; 7:13665.
    • BRAF
    • R2 Yaeger R, Kotani D, Mondaca S, Parikh AR, Bando H, Van Seventer EE, Taniguchi H, Zhao H, Thant CN, de Stanchina E, Rosen N, Corcoran RB, Yoshino T, Yao Z, Ebi H. Response to Anti-EGFR Therapy in Patients with BRAF non-V600-Mutant Metastatic Colorectal Cancer. Clin Cancer Res 2019; 25:7089-7097.
    • KRAS
    • R2 Favazza LA, Parseghian CM, Kaya C, Nikiforova MN, Roy S, Wald AI, Landau MS, Proksell SS, Dueker JM, Johnston ER, Brand RE, Bahary N, Gorantla VC, Rhee JC, Pingpank JF, Choudry HA, Lee K, Paniccia A, Ongchin MC, Zureikat AH, Bartlett DL, Singhi AD. KRAS amplification in metastatic colon cancer is associated with a history of inflammatory bowel disease and may confer resistance to anti-EGFR therapy. Mod Pathol 2020; 33:1832-1843.
    • KRAS+NRAS
    • 1 Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351:337-45.
    • 1 Sorich MJ, Wiese MD, Rowland A, Kichenadasse G, McKinnon RA, Karapetis CS. Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized, controlled trials. Ann Oncol 2015; 26:13-21.
    • EGFR
    • 4 Sabatier R, Lopez M, Guille A, Billon E, Carbuccia N, Garnier S, Adelaide J, Extra J, Cappiello M, Charafe-Jauffret E, Pakradouni J, Viens P, Gonçalves A, Chaffanet M, Birnbaum D, Bertucci F. High Response to Cetuximab in a Patient With EGFR-Amplified Heavily Pretreated Metastatic Triple-Negative Breast Cancer. JCO Prec Oncol 2018; 10.1200/PO.18.00310 - published online April 3, 2019
    • 4 Maron SB, Alpert L, Kwak HA, Lomnicki S, Chase L, Xu D, O'Day E, Nagy RJ, Lanman RB, Cecchi F, Hembrough T, Schrock A, Hart J, Xiao SY, Setia N, Catenacci DVT. Targeted Therapies for Targeted Populations: Anti-EGFR Treatment for EGFR-Amplified Gastroesophageal Adenocarcinoma. Cancer Discov 2018; 8:696-713.
    • BRAF
    • 4 Yaeger R, Kotani D, Mondaca S, Parikh AR, Bando H, Van Seventer EE, Taniguchi H, Zhao H, Thant CN, de Stanchina E, Rosen N, Corcoran RB, Yoshino T, Yao Z, Ebi H. Response to Anti-EGFR Therapy in Patients with BRAF non-V600-Mutant Metastatic Colorectal Cancer. Clin Cancer Res 2019; 25:7089-7097.
    • EGFR
    • 4 Maron SB, Moya S, Morano F, Emmett MJ, Chou JF, Sabwa S, Walch H, Peterson B, Schrock AB, Zhang L, Janjigian YY, Chalasani S, Ku GY, Disel U, Enzinger P, Uboha N, Kato S, Yoshino T, Shitara K, Nakamura Y, Saeed A, Kasi P, Chao J, Lee J, Capanu M, Wainberg Z, Petty R, Pietrantonio F, Klempner SJ, Catenacci DVT. Epidermal Growth Factor Receptor Inhibition in Epidermal Growth Factor Receptor-Amplified Gastroesophageal Cancer: Retrospective Global Experience. J Clin Oncol 2022 Mar 29:JCO2102453. [Epub ahead of print]
    • Cetuximab + FOLFIRI
    • KRAS, NRAS
    • R1 Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008; 359:1757-65.
    • BRAF
    • R1 De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F, Rougier P, Vincenzi B, Santini D, Tonini G, Cappuzzo F, Frattini M, Molinari F, Saletti P, De Dosso S, Martini M, Bardelli A, Siena S, Sartore-Bianchi A, Tabernero J, Macarulla T, Di Fiore F, Gangloff AO, Ciardiello F, Pfeiffer P, Qvortrup C, Hansen TP, Van Cutsem E, Piessevaux H, Lambrechts D, Delorenzi M, Tejpar S. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol 2010; 11:753-62.
    • KRAS, NRAS
    • R1 Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 2013; 369:1023-34.
    • HRAS
    • R2 Boidot R, Chevrier S, Julie V, Ladoire S, Ghiringhelli F. HRAS G13D, a new mutation implicated in the resistance to anti-EGFR therapies in colorectal cancer, a case report. Int J Colorectal Dis 2016; 31:1245-6.
    • KRAS+NRAS
    • 1 Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351:337-45.
    • 1 Sorich MJ, Wiese MD, Rowland A, Kichenadasse G, McKinnon RA, Karapetis CS. Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized, controlled trials. Ann Oncol 2015; 26:13-21.
    • Cetuximab + Irinotecan
    • KRAS, NRAS
    • R1 Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008; 359:1757-65.
    • BRAF
    • R1 De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F, Rougier P, Vincenzi B, Santini D, Tonini G, Cappuzzo F, Frattini M, Molinari F, Saletti P, De Dosso S, Martini M, Bardelli A, Siena S, Sartore-Bianchi A, Tabernero J, Macarulla T, Di Fiore F, Gangloff AO, Ciardiello F, Pfeiffer P, Qvortrup C, Hansen TP, Van Cutsem E, Piessevaux H, Lambrechts D, Delorenzi M, Tejpar S. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol 2010; 11:753-62.
    • KRAS, NRAS
    • R1 Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 2013; 369:1023-34.
    • ERBB2
    • R2 Raghav K, Loree JM, Morris JS, Overman MJ, Yu R, Meric-Bernstam F, Menter D, Korphaisarn K, Kee B, Muranyi A, Singh S, Routbort M, Chen K, Shaw KR, Katkhuda R, Shanmugam K, Maru D, Fakih M, Kopetz S. Validation of HER2 Amplification as a Predictive Biomarker for Anti-Epidermal Growth Factor Receptor Antibody Therapy in Metastatic Colorectal Cancer. JCO Prec Oncol 2018; - published online January 22, 2019
    • HRAS
    • R2 Boidot R, Chevrier S, Julie V, Ladoire S, Ghiringhelli F. HRAS G13D, a new mutation implicated in the resistance to anti-EGFR therapies in colorectal cancer, a case report. Int J Colorectal Dis 2016; 31:1245-6.
    • KRAS
    • R2 Segelov E, Thavaneswaran S, Waring PM, Desai J, Robledo KP, Gebski VJ, Elez E, Nott LM, Karapetis CS, Lunke S, Chantrill LA, Pavlakis N, Khasraw M, Underhill C, Ciardiello F, Jefford M, Wasan H, Haydon A, Price TJ, van Hazel G, Wilson K, Simes J, Shapiro JD. Response to Cetuximab With or Without Irinotecan in Patients With Refractory Metastatic Colorectal Cancer Harboring the KRAS G13D Mutation: Australasian Gastro-Intestinal Trials Group ICECREAM Study. J Clin Oncol 2016; 34:2258-64.
    • KRAS+NRAS
    • 1 Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351:337-45.
    • 1 Sorich MJ, Wiese MD, Rowland A, Kichenadasse G, McKinnon RA, Karapetis CS. Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized, controlled trials. Ann Oncol 2015; 26:13-21.
    • Cetuximab + Irinotecan + Vemurafenib
    • BRAF
    • 3 Kopetz S, Guthrie KA, Morris VK, Lenz HJ, Magliocco AM, Maru D, Yan Y, Lanman R, Manyam G, Hong DS, Sorokin A, Atreya CE, Diaz LA, Allegra C, Raghav KP, Wang SE, Lieu CH, McDonough SL, Philip PA, Hochster HS. Randomized Trial of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF-Mutant Metastatic Colorectal Cancer (SWOG S1406). J Clin Oncol 2020 Dec 23:JCO2001994. [Epub ahead of print]
    • Cisplatin
    • SMARCA4
    • R2 Xue Y, Morris JL, Yang K, Fu Z, Zhu X, Johnson F, Meehan B, Witkowski L, Yasmeen A, Golenar T, Coatham M, Morin G, Monast A, Pilon V, Fiset PO, Jung S, Gonzalez AV, Camilleri-Broet S, Fu L, Postovit LM, Spicer J, Gotlieb WH, Guiot MC, Rak J, Park M, Lockwood W, Foulkes WD, Prudent J, Huang S. SMARCA4/2 loss inhibits chemotherapy-induced apoptosis by restricting IP3R3-mediated Ca2+ flux to mitochondria. Nat Commun 2021; 12:5404.
    • Chromosome
    • R2 Timmerman DM, Eleveld TF, Sriram S, Dorssers LCJ, Gillis AJM, Schmidtova S, Kalavska K, van de Werken HJG, Oing C, Honecker F, Mego M, Looijenga LHJ. Chromosome 3p25.3 Gain Is Associated With Cisplatin Resistance and Is an Independent Predictor of Poor Outcome in Male Malignant Germ Cell Tumors. J Clin Oncol 2022 Apr 20:JCO2102809. [Epub ahead of print]
    • ERCC1
    • 4 Reed E. ERCC1 and clinical resistance to platinum-based therapy. Clin Cancer Res 2005; 11:6100-2.
    • 4 Steffensen KD, Waldstrøm M, Jakobsen A. The relationship of platinum resistance and ERCC1 protein expression in epithelial ovarian cancer. Int J Gynecol Cancer 2009; 19:820-5.
    • 4 Zimling ZG, Sørensen JB, Gerds TA, Bech C, Andersen CB, Santoni-Rugiu E. Low ERCC1 expression in malignant pleural mesotheliomas treated with cisplatin and vinorelbine predicts prolonged progression-free survival. J Thorac Oncol 2012; 7:249-56.
    • CDK12
    • 4 Joshi PM, Sutor SL, Huntoon CJ, Karnitz LM. Ovarian cancer-associated mutations disable catalytic activity of CDK12, a kinase that promotes homologous recombination repair and resistance to cisplatin and poly(ADP-ribose) polymerase inhibitors. J Biol Chem 2014; 289:9247-53.
    • ERCC2
    • 4 Van Allen EM, Mouw KW, Kim P, Iyer G, Wagle N, Al-Ahmadie H, Zhu C, Ostrovnaya I, Kryukov GV, O'Connor KW, Sfakianos J, Garcia-Grossman I, Kim J, Guancial EA, Bambury R, Bahl S, Gupta N, Farlow D, Qu A, Signoretti S, Barletta JA, Reuter V, Boehm J, Lawrence M, Getz G, Kantoff P, Bochner BH, Choueiri TK, Bajorin DF, Solit DB, Gabriel S, D'Andrea A, Garraway LA, Rosenberg JE. Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma. Cancer Discov 2014; 4:1140-53.
    • Homologous Recombination Deficiency Score
    • 4 Telli ML, Timms KM, Reid J, Hennessy B, Mills GB, Jensen KC, Szallasi Z, Barry WT, Winer EP, Tung NM, Isakoff SJ, Ryan PD, Greene-Colozzi A, Gutin A, Sangale Z, Iliev D, Neff C, Abkevich V, Jones JT, Lanchbury JS, Hartman AR, Garber JE, Ford JM, Silver DP, Richardson AL. Homologous Recombination Deficiency (HRD) Score Predicts Response to Platinum-Containing Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer. Clin Cancer Res 2016; 22:3764-73.
    • ERCC2
    • 4 Zhao H, Yu X, Ding Y, Zhao J, Wang G, Wu X, Jiang J, Peng C, Guo GZ, Cui S. MiR-770-5p inhibits cisplatin chemoresistance in human ovarian cancer by targeting ERCC2. Oncotarget 2016; 7:53254-53268.
    • 4 Zhang G, Guan Y, Zhao Y, van der Straaten T, Xiao S, Xue P, Zhu G, Liu Q, Cai Y, Jin C, Yang J, Wu S, Lu X. ERCC2/XPD Lys751Gln alter DNA repair efficiency of platinum-induced DNA damage through P53 pathway. Chem Biol Interact 2017; 263:55-65.
    • ERCC1
    • 4 Karageorgopoulou S, Kostakis ID, Gazouli M, Markaki S, Papadimitriou M, Bournakis E, Dimopoulos MA, Papadimitriou CA. Prognostic and predictive factors in patients with metastatic or recurrent cervical cancer treated with platinum-based chemotherapy. BMC Cancer 2017; 17:451.
    • FANCA
    • 4 Wilkes DC, Sailer V, Xue H, Cheng H, Collins CC, Gleave M, Wang Y, Demichelis F, Beltran H, Rubin MA, Rickman DS. A germline FANCA alteration that is associated with increased sensitivity to DNA damaging agents. Cold Spring Harb Mol Case Stud 2017; 3(5). pii: a001487.
    • ERCC2
    • 4 Li Q, Damish AW, Frazier Z, Liu D, Reznichenko E, Kamburov A, Bell A, Zhao H, Jordan EJ, Gao SP, Ma J, Abbosh PH, Bellmunt J, Plimack ER, Lazaro JB, Solit DB, Bajorin D, Rosenberg JE, D'Andrea AD, Riaz N, Van Allen EM, Iyer G, Mouw KW. ERCC2 Helicase Domain Mutations Confer Nucleotide Excision Repair Deficiency and Drive Cisplatin Sensitivity in Muscle-Invasive Bladder Cancer. Clin Cancer Res 2019; 25:977-988.
    • 4 Pietzak EJ, Zabor EC, Bagrodia A, Armenia J, Hu W, Zehir A, Funt S, Audenet F, Barron D, Maamouri N, Li Q, Teo MY, Arcila ME, Berger MF, Schultz N, Dalbagni G, Herr HW, Bajorin DF, Rosenberg JE, Al-Ahmadie H, Bochner BH, Solit DB, Iyer G. Genomic Differences Between "Primary" and "Secondary" Muscle-invasive Bladder Cancer as a Basis for Disparate Outcomes to Cisplatin-based Neoadjuvant Chemotherapy. Eur Urol 2019; 75:231-239.
    • EMSY
    • 4 Hollis RL, Churchman M, Michie CO, Rye T, Knight L, McCavigan A, Perren T, Williams ARW, McCluggage WG, Kaplan RS, Jayson GC, Oza A, Harkin DP, Herrington CS, Kennedy R, Gourley C. High EMSY expression defines a BRCA-like subgroup of high-grade serous ovarian carcinoma with prolonged survival and hypersensitivity to platinum. Cancer 2019; 125:2772-2781.
    • ERCC1
    • 4 Fukumoto SI, Oizumi S, Harada M, Sukoh N, Nakano K, Fuke S, Sakakibara-Konishi J, Takamura K, Ito K, Fujita Y, Nishigaki Y, Harada T, Akie K, Kinoshita I, Amano T, Isobe H, Dosaka-Akita H, Nishimura M; Hokkaido Lung Cancer Clinical Study Group. A randomized phase II trial of cisplatin plus gemcitabine versus carboplatin plus gemcitabine in patients with completely resected non-small cell lung cancer: Hokkaido Lung Cancer Clinical Study Group Trial (HOT0703). Cancer Chemother Pharmacol 2020; 86:117-127.
    • Cisplatin + Gemcitabine
    • BRCA1, BRCA2, PALB2
    • 3 O'Reilly EM, Lee JW, Zalupski M, Capanu M, Park J, Golan T, Tahover E, Lowery MA, Chou JF, Sahai V, Brenner R, Kindler HL, Yu KH, Zervoudakis A, Vemuri S, Stadler ZK, Do RKG, Dhani N, Chen AP, Kelsen DP. Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation. J Clin Oncol 2020; 38:1378-1388.
    • Cisplatin + Veliparib
    • BRCA1, BRCA2
    • 3 Sharma P, Rodler E, Barlow WE, Gralow J, Huggins-Puhalla SL, Anders CK, Goldstein LJ, Brown-Glaberman UA, Huynh T, Szyarto CS, Godwin AK, Pathak HB, Swisher EM, Radke MR, Timms KM, Lew DL, Miao J, Pusztai L, Hayes DF, Hortobagyi GN. Results of a phase II randomized trial of cisplatin +/- veliparib in metastatic triple-negative breast cancer (TNBC) and/or germline BRCA-associated breast cancer (SWOG S1416). J Clin Oncol 2020; 38(15_suppl): 1001-1001.
    • Cobimetinib
    • BRAF, KRAS, MAP2K1, MAP2K2, NRAS, RAF1
    • 3 Diamond EL, Durham BH, Ulaner GA, Drill E, Buthorn J, Ki M, Bitner L, Cho H, Young RJ, Francis JH, Rampal R, Lacouture M, Brody LA, Ozkaya N, Dogan A, Rosen N, Iasonos A, Abdel-Wahab O, Hyman DM. Efficacy of MEK inhibition in patients with histiocytic neoplasms. Nature 2019; 567:521-524.
    • RAF1
    • 4 Touat M, Younan N, Euskirchen P, Fontanilles M, Mokhtari K, Dehais C, Tilleul P, Rahimian-Aghda A, Resnick A, Gimenez-Roqueplo A, Blons H, Hoang-Xuan K, Delattre J, Idbaih A, Laurent-Puig P, Sanson M. Successful Targeting of an ATG7-RAF1 Gene Fusion in Anaplastic Pleomorphic Xanthoastrocytoma With Leptomeningeal Dissemination. JCO Prec Oncol 2018; 10.1200/PO.18.00298 - published online March 21, 2019
    • BRAF
    • 4 Hatzivassiliou G, Haling JR, Chen H, Song K, Price S, Heald R, Hewitt JF, Zak M, Peck A, Orr C, Merchant M, Hoeflich KP, Chan J, Luoh SM, Anderson DJ, Ludlam MJ, Wiesmann C, Ultsch M, Friedman LS, Malek S, Belvin M. Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers. Nature 2013; 501:232-6.
    • HRAS
    • 4 Kiessling MK, Curioni-Fontecedro A, Samaras P, Atrott K, Cosin-Roger J, Lang S, Scharl M, Rogler G. Mutant HRAS as novel target for MEK and mTOR inhibitors. Oncotarget 2015; 6:42183-96.
    • KRAS
    • 4 Jacobsen E, Shanmugam V, Jagannathan J. Rosai-Dorfman Disease with Activating KRAS Mutation - Response to Cobimetinib. N Engl J Med 2017; 377:2398-2399.
    • RAF1
    • 4 McEvoy CR, Xu H, Smith K, Etemadmoghadam D, San Leong H, Choong DY, Byrne DJ, Iravani A, Beck S, Mileshkin L, Tothill RW, Bowtell DD, Bates BM, Nastevski V, Browning J, Bell AH, Khoo C, Desai J, Fellowes AP, Fox SB, Prall OW. Profound MEK inhibitor response in a cutaneous melanoma harboring a GOLGA4-RAF1 fusion. J Clin Invest 2019; 129:1940-1945.
    • ARAF
    • 4 Diamond EL, Durham BH, Ulaner GA, Drill E, Buthorn J, Ki M, Bitner L, Cho H, Young RJ, Francis JH, Rampal R, Lacouture M, Brody LA, Ozkaya N, Dogan A, Rosen N, Iasonos A, Abdel-Wahab O, Hyman DM. Efficacy of MEK inhibition in patients with histiocytic neoplasms. Nature 2019; 567:521-524.
    • MAP2K1
    • 4 Lian T, Li C, Wang H. Trametinib in the treatment of multiple malignancies harboring MEK1 mutations. Cancer Treat Rev 2019; 81:101907.
    • Copanlisib
    • PIK3CA
    • 3 Damodaran S, Zhao F, Deming DA, Mitchell EP, Wright JJ, Doyle LA, Gray RJ, Li S, McShane L, Rubinstein LV, Patton DR, Williams M, Hamilton SR, Suga JM, Conley BA, Arteaga CL, Harris L, O'Dwyer PJ, Chen AP, Flaherty K. Phase II study of copanlisib in patients with tumors with PIK3CA mutations (PTEN loss allowed): NCI MATCH EAY131-Z1F. J Clin Oncol 2020; 38(15_suppl): 3506-3506.
    • 3 Damodaran S, Zhao F, Deming DA, Mitchell EP, Wright JJ, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton DR, Williams PM, Hamilton SR, Suga JM, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of Copanlisib in Patients With Tumors With PIK3CA Mutations: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1F. J Clin Oncol 2022 Feb 8:JCO2101648. [Epub ahead of print]
    • Crizotinib
    • ALK
    • R2 J. Jean Cui, Evan Rogers, Dayong Zhai, Wei Deng, Jane Ung, Vivian Nguyen, Han Zhang, Xin Zhang, Ana Parra, Maria Barrera, Dong Lee, Brion Murray. TPX-0131: A next generation macrocyclic ALK inhibitor that overcomes ALK resistant mutations refractory to current approved ALK inhibitors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5226.
    • R2 Sasaki T, Okuda K, Zheng W, Butrynski J, Capelletti M, Wang L, Gray NS, Wilner K, Christensen JG, Demetri G, Shapiro GI, Rodig SJ, Eck MJ, Jänne PA. The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers. Cancer Res 2010; 70:10038-43.
    • R2 Katayama R, Shaw AT, Khan TM, Mino-Kenudson M, Solomon BJ, Halmos B, Jessop NA, Wain JC, Yeo AT, Benes C, Drew L, Saeh JC, Crosby K, Sequist LV, Iafrate AJ, Engelman JA. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci Transl Med 2012; 4:120ra17.
    • R2 Lovly CM, Pao W. Escaping ALK inhibition: mechanisms of and strategies to overcome resistance. Sci Transl Med 2012; 4:120ps2.
    • ROS1
    • R2 Davare MA, Vellore NA, Wagner JP, Eide CA, Goodman JR, Drilon A, Deininger MW, O'Hare T, Druker BJ. Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors. Proc Natl Acad Sci U S A 2015; 112:E5381-90.
    • ALK
    • R2 Hatcher JM, Bahcall M, Choi HG, Gao Y, Sim T, George R, Jänne PA, Gray NS. Discovery of Inhibitors That Overcome the G1202R Anaplastic Lymphoma Kinase Resistance Mutation. J Med Chem 2015; 58:9296-9308.
    • R2 Shaw AT, Friboulet L, Leshchiner I, Gainor JF, Bergqvist S, Brooun A, Burke BJ, Deng YL, Liu W, Dardaei L, Frias RL, Schultz KR, Logan J, James LP, Smeal T, Timofeevski S, Katayama R, Iafrate AJ, Le L, McTigue M, Getz G, Johnson TW, Engelman JA. Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F. N Engl J Med 2016; 374:54-61.
    • MET
    • R2 Heist RS, Sequist LV, Borger D, Gainor JF, Arellano RS, Le LP, Dias-Santagata D, Clark JW, Engelman JA, Shaw AT, Iafrate AJ. Acquired Resistance to Crizotinib in NSCLC with MET Exon 14 Skipping. J Thorac Oncol 2016; 11:1242-1245.
    • R2 Ou SI, Young L, Schrock AB, Johnson A, Klempner SJ, Zhu VW, Miller VA, Ali SM. Emergence of Preexisting MET Y1230C Mutation as a Resistance Mechanism to Crizotinib in NSCLC with MET Exon 14 Skipping. J Thorac Oncol 2017; 12:137-140.
    • R2 Dong HJ, Li P, Wu CL, Zhou XY, Lu HJ, Zhou T. Response and acquired resistance to crizotinib in Chinese patients with lung adenocarcinomas harboring MET Exon 14 splicing alternations. Lung Cancer 2016; 102:118-121.
    • ALK
    • R2 Holla VR, Elamin YY, Bailey AM, Johnson AM, Litzenburger BC, Khotskaya YB, Sanchez NS, Zeng J, Shufean MA, Shaw KR, Mendelsohn J, Mills GB, Meric-Bernstam F, Simon GR. ALK: a tyrosine kinase target for cancer therapy. Cold Spring Harb Mol Case Stud 2017; 3:a001115.
    • R2 Lin JJ, Riely GJ, Shaw AT. Targeting ALK: Precision Medicine Takes on Drug Resistance. Cancer Discov 2017; 7:137-155.
    • MET
    • R2 Lu X, Peled N, Greer J, Wu W, Choi P, Berger AH, Wong S, Jen KY, Seo Y, Hann B, Brooks A, Meyerson M, Collisson EA. MET Exon 14 Mutation Encodes an Actionable Therapeutic Target in Lung Adenocarcinoma. Cancer Res 2017; 77:4498-4505.
    • R2 Schrock AB, Lai A, Ali SM, Miller VA, Raez LE. Mutation of MET Y1230 as an Acquired Mechanism of Crizotinib Resistance in NSCLC with MET Exon 14 Skipping. J Thorac Oncol 2017; 12:e89-e90.
    • R2 Zhang Y, Yin J, Peng F. Acquired resistance to crizotinib in advanced lung adenocarcinoma with MET exon 14 skipping. Lung Cancer 2017; 113:69-71.
    • R2 Jiang W, Yang N, Zhang Y. Novel MET Exon 14 Skipping Treatment-Naïve Lung Adenocarcinoma Presented Primary Resistance to Crizotinib. J Thorac Oncol 2018; 13:e124-e126.
    • KRAS+MET
    • R2 Suzawa K, Offin M, Lu D, Kurzatkowski C, Vojnic M, Smith RS, Sabari JK, Tai H, Mattar M, Khodos I, de Stanchina E, Rudin CM, Kris MG, Arcila ME, Lockwood WW, Drilon A, Ladanyi M, Somwar R. Activation of KRAS Mediates Resistance to Targeted Therapy in MET Exon 14-mutant Non-small Cell Lung Cancer. Clin Cancer Res 2019; 25:1248-1260.
    • ALK
    • R2 Zhu VW, Schrock AB, Bosemani T, Benn BS, Ali SM, Ou SI. Dramatic response to alectinib in a lung cancer patient with a novel VKORC1L1-ALK fusion and an acquired ALK T1151K mutation. Lung Cancer (Auckl) 2018; 9:111-116. eCollection 2018.
    • R2 Shaw AT, Solomon BJ, Besse B, Bauer TM, Lin CC, Soo RA, Riely GJ, Ou SI, Clancy JS, Li S, Abbattista A, Thurm H, Satouchi M, Camidge DR, Kao S, Chiari R, Gadgeel SM, Felip E, Martini JF. ALK Resistance Mutations and Efficacy of Lorlatinib in Advanced Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer. J Clin Oncol 2019; 37:1370-1379.
    • ROS1
    • R2 Guisier F, Piton N, Salaun M, Thiberville L. ROS1-rearranged NSCLC With Secondary Resistance Mutation: Case Report and Current Perspectives. Clin Lung Cancer 2019; 20:e593-e596.
    • EGFR, KRAS, MET, MET+TP53, NF1
    • R2 Rotow JK, Gui P, Wu W, Raymond VM, Lanman RB, Kaye FJ, Peled N, Fece de la Cruz F, Nadres B, Corcoran RB, Yeh I, Bastian BC, Starostik P, Newsom K, Olivas VR, Wolff AM, Fraser JS, Collisson EA, McCoach CE, Camidge DR, Pacheco J, Bazhenova L, Li T, Bivona TG, Blakely CM. Co-occurring Alterations in the RAS-MAPK Pathway Limit Response to MET Inhibitor Treatment in MET Exon 14 Skipping Mutation-Positive Lung Cancer. Clin Cancer Res 2020; 26:439-449.
    • MET
    • R2 Wiesweg M, Herold T, Metzenmacher M, Eberhardt WE, Reis H, Darwiche K, Aigner C, Stuschke M, Herrmann K, Nensa F, Schildhaus HU, Schuler M. Clinical response to crizotinib and emergence of resistance in lung adenocarcinoma harboring a MET c-Cbl binding site mutation. Lung Cancer 2020; 139:165-168.
    • EGFR, KRAS, MET
    • R2 Recondo G, Bahcall M, Spurr LF, Che J, Ricciuti B, Leonardi GC, Lo YC, Li YY, Lamberti G, Nguyen T, Milan MSD, Venkatraman D, Umeton R, Paweletz CP, Albayrak A, Cherniack AD, Price KS, Fairclough SR, Nishino M, Sholl LM, Oxnard GR, Jänne PA, Awad MM. Molecular Mechanisms of Acquired Resistance to MET Tyrosine Kinase Inhibitors in Patients with MET Exon 14-Mutant NSCLC. Clin Cancer Res 2020; 26:2615-2625.
    • MET
    • R2 Parsons BM, Meier DR, Richmond CS, Gurda GT, Lofgren KA, Burkard ME, Deming DA, Kenny PA. Acquisition of Cabozantinib-Sensitive MET D1228N Mutation During Progression on Crizotinib in MET-Amplified Triple-Negative Breast Cancer. Clin Breast Cancer 2020; 20:e433-e438.
    • R2 Huang C, Zou Q, Liu H, Qiu B, Li Q, Lin Y, Liang Y. Management of Non-small Cell Lung Cancer Patients with MET Exon 14 Skipping Mutations. Curr Treat Options Oncol 2020; 21:33.
    • ROS1+MET
    • R2 Wang Y, Chen Z, Han X, Li J, Guo H, Shi J. Acquired MET D1228N Mutations Mediate Crizotinib Resistance in Lung Adenocarcinoma with ROS1 Fusion: A Case Report. Oncologist 2021; 26:178-181.
    • ALK
    • R2 Foster JH, Voss SD, Hall DC, Minard CG, Balis FM, Wilner K, Berg SL, Fox E, Adamson PC, Blaney S, Weigel BJ, Mossé YP. Activity of Crizotinib in Patients with ALK-aberrant Relapsed/Refractory Neuroblastoma: A Children's Oncology Group Study (ADVL0912). Clin Cancer Res 2021 Feb 10. pii: clincanres.4224.2020. [Epub ahead of print]
    • ALK
    • 1 Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Jänne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010; 363:1693-703.
    • ROS1
    • 1 Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, Riely GJ, Varella-Garcia M, Shapiro GI, Costa DB, Doebele RC, Le LP, Zheng Z, Tan W, Stephenson P, Shreeve SM, Tye LM, Christensen JG, Wilner KD, Clark JW, Iafrate AJ. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med 2014; 371:1963-71.
    • ALK
    • 1 Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Iyer S, Reisman A, Wilner KD, Tursi J, Blackhall F; PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med 2014; 371:2167-77.
    • ALK
    • 2 Butrynski JE, D'Adamo DR, Hornick JL, Dal Cin P, Antonescu CR, Jhanwar SC, Ladanyi M, Capelletti M, Rodig SJ, Ramaiya N, Kwak EL, Clark JW, Wilner KD, Christensen JG, Jänne PA, Maki RG, Demetri GD, Shapiro GI. Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor. N Engl J Med 2010; 363:1727-33.
    • 2 Balis FM, Thompson PA, Mosse YP, Blaney SM, Minard CG, Weigel BJ, Fox E. First-dose and steady-state pharmacokinetics of orally administered crizotinib in children with solid tumors: a report on ADVL0912 from the Children's Oncology Group Phase 1/Pilot Consortium. Cancer Chemother Pharmacol 2017; 79:181-187.
    • 2 Gambacorti-Passerini C, Orlov S, Zhang L, Braiteh F, Huang H, Esaki T, Horibe K, Ahn JS, Beck JT, Edenfield WJ, Shi Y, Taylor M, Tamura K, Van Tine BA, Wu SJ, Paolini J, Selaru P, Kim TM. Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC): A phase 1b open-label study. Am J Hematol 2018; 93:607-614.
    • MET
    • 3 Camidge DR, Ou SI, Shapiro G, Otterson GA, Villaruz LC, Villalona-Calero MA, Iafrate AJ, Varella-Garcia M, Dacic S, Cardarella S, Zhao W, Tye L, Stephenson P, Wilner KD, James LP, Socinski MA. Efficacy and safety of crizotinib in patients with advanced c-MET-amplified non-small cell lung cancer (NSCLC). J Clin Oncol 2014; 32(15_suppl): 8001-8001.
    • ALK
    • 3 Shaw AT, Friboulet L, Leshchiner I, Gainor JF, Bergqvist S, Brooun A, Burke BJ, Deng YL, Liu W, Dardaei L, Frias RL, Schultz KR, Logan J, James LP, Smeal T, Timofeevski S, Katayama R, Iafrate AJ, Le L, McTigue M, Getz G, Johnson TW, Engelman JA. Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F. N Engl J Med 2016; 374:54-61.
    • MET
    • 3 Awad MM, Oxnard GR, Jackman DM, Savukoski DO, Hall D, Shivdasani P, Heng JC, Dahlberg SE, Jänne PA, Verma S, Christensen J, Hammerman PS, Sholl LM. MET Exon 14 Mutations in Non-Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression. J Clin Oncol 2016; 34:721-30.
    • ALK
    • 3 Lin JJ, Riely GJ, Shaw AT. Targeting ALK: Precision Medicine Takes on Drug Resistance. Cancer Discov 2017; 7:137-155.
    • MET, ROS1
    • 3 Landi L, Chiari R, Tiseo M, D'Incà F, Dazzi C, Chella A, Delmonte A, Bonanno L, Giannarelli D, Cortinovis DL, de Marinis F, Borra G, Morabito A, Gridelli C, Galetta D, Barbieri F, Grossi F, Capelletto E, Minuti G, Mazzoni F, Verusio C, Bria E, Alì G, Bruno R, Proietti A, Fontanini G, Crinò L, Cappuzzo F. Crizotinib in MET-Deregulated or ROS1-Rearranged Pretreated Non-Small Cell Lung Cancer (METROS): A Phase II, Prospective, Multicenter, Two-Arms Trial. Clin Cancer Res 2019; 25:7312-7319.
    • MET
    • 3 Drilon A, Clark JW, Weiss J, Ou SI, Camidge DR, Solomon BJ, Otterson GA, Villaruz LC, Riely GJ, Heist RS, Awad MM, Shapiro GI, Satouchi M, Hida T, Hayashi H, Murphy DA, Wang SC, Li S, Usari T, Wilner KD, Paik PK. Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration. Nat Med 2020; 26:47-51.
    • ALK
    • 3 Foster JH, Voss SD, Hall DC, Minard CG, Balis FM, Wilner K, Berg SL, Fox E, Adamson PC, Blaney S, Weigel BJ, Mossé YP. Activity of Crizotinib in Patients with ALK-aberrant Relapsed/Refractory Neuroblastoma: A Children's Oncology Group Study (ADVL0912). Clin Cancer Res 2021 Feb 10. pii: clincanres.4224.2020. [Epub ahead of print]
    • MET
    • 3 Camidge DR, Otterson GA, Clark JW, Ignatius Ou SH, Weiss J, Ades S, Shapiro GI, Socinski MA, Murphy DA, Conte U, Tang Y, Wang SC, Wilner KD, Villaruz LC. Crizotinib in Patients With MET-Amplified NSCLC. J Thorac Oncol 2021; 16:1017-1029.
    • 3 Aparicio T, Cozic N, de la Fouchardière C, Meriaux E, Plaza J, Mineur L, Guimbaud R, Samalin E, Mary F, Lecomte T, Gomez-Roca C, Haineaux PA, Gratet A, Selves J, Menu Y, Colignon N, Johnson L, Legrand F, Vassal G. The Activity of Crizotinib in Chemo-Refractory MET-Amplified Esophageal and Gastric Adenocarcinomas: Results from the AcSé-Crizotinib Program. Target Oncol 2021; 16:381-388.
    • ALK
    • 4 Hu C, Zhao L, Wu F. Different response to ALK inhibitors in EML4-ALK positive mediastinal cancer of unknown primary. J Clin Oncol 2020; 38(15_suppl): 104-104.
    • MET
    • 4 Lennerz JK, Kwak EL, Ackerman A, Michael M, Fox SB, Bergethon K, Lauwers GY, Christensen JG, Wilner KD, Haber DA, Salgia R, Bang YJ, Clark JW, Solomon BJ, Iafrate AJ. MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib. J Clin Oncol 2011; 29:4803-10.
    • MET+KRAS
    • 4 Palma NA, Ali SM, O'Connor J, Dutta D, Wang K, Soman S, Palmer GA, Morosini D, Ross JS, Lipson D, Stephens PJ, Patel M, Miller VA, Koutrelakos N. Durable Response to Crizotinib in a MET-Amplified, KRAS-Mutated Carcinoma of Unknown Primary. Case Rep Oncol 2014; 7:503-8. eCollection 2014 May.
    • MET
    • 4 Waqar SN, Morgensztern D, Sehn J. MET Mutation Associated with Responsiveness to Crizotinib. J Thorac Oncol 2015; 10:e29-e31.
    • 4 Frampton GM, Ali SM, Rosenzweig M, Chmielecki J, Lu X, Bauer TM, Akimov M, Bufill JA, Lee C, Jentz D, Hoover R, Ou SH, Salgia R, Brennan T, Chalmers ZR, Jaeger S, Huang A, Elvin JA, Erlich R, Fichtenholtz A, Gowen KA, Greenbowe J, Johnson A, Khaira D, McMahon C, Sanford EM, Roels S, White J, Greshock J, Schlegel R, Lipson D, Yelensky R, Morosini D, Ross JS, Collisson E, Peters M, Stephens PJ, Miller VA. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov 2015; 5:850-9.
    • ALK
    • 4 Maxson JE, Davare MA, Luty SB, Eide CA, Chang BH, Loriaux MM, Tognon CE, Bottomly D, Wilmot B, McWeeney SK, Druker BJ, Tyner JW. Therapeutically Targetable ALK Mutations in Leukemia. Cancer Res 2015; 75:2146-50.
    • MET
    • 4 Shea M, Huberman MS, Costa DB. Lazarus-Type Response to Crizotinib in a Patient with Poor Performance Status and Advanced MET Exon 14 Skipping Mutation-Positive Lung Adenocarcinoma. J Thorac Oncol 2016; 11:e81-2.
    • 4 Mahjoubi L, Gazzah A, Besse B, Lacroix L, Soria JC. A never-smoker lung adenocarcinoma patient with a MET exon 14 mutation (D1028N) and a rapid partial response after crizotinib. Invest New Drugs 2016; 34:397-8.
    • 4 [No authors listed] . Correction: Response to MET Inhibitors in Patients with Stage IV Lung Adenocarcinomas Harboring MET Mutations Causing Exon 14 Skipping. Cancer Discov 2016; 6:330.
    • 4 Heist RS, Shim HS, Gingipally S, Mino-Kenudson M, Le L, Gainor JF, Zheng Z, Aryee M, Xia J, Jia P, Jin H, Zhao Z, Pao W, Engelman JA, Iafrate AJ. MET Exon 14 Skipping in Non-Small Cell Lung Cancer. Oncologist 2016; 21:481-6.
    • 4 International Cancer Genome Consortium PedBrain Tumor Project. Recurrent MET fusion genes represent a drug target in pediatric glioblastoma. Nat Med 2016; 22:1314-1320.
    • ALK
    • 4 Ross JS, Ali SM, Fasan O, Block J, Pal S, Elvin JA, Schrock AB, Suh J, Nozad S, Kim S, Jeong Lee H, Sheehan CE, Jones DM, Vergilio JA, Ramkissoon S, Severson E, Daniel S, Fabrizio D, Frampton G, Miller VA, Stephens PJ, Gay LM. ALK Fusions in a Wide Variety of Tumor Types Respond to Anti-ALK Targeted Therapy. Oncologist 2017; 22:1444-1450.
    • ROS1
    • 4 Dong L, Xia J, Zhang J, Zhang Y, Zhu N, Zhang P, Zhang Y, Zhang X, Li S. Long-term progression-free survival in an advanced lung adenocarcinoma patient harboring EZR-ROS1 rearrangement: a case report. BMC Pulm Med 2018; 18:13.
    • MET
    • 4 Davies KD, Ng TL, Estrada-Bernal A, Le AT, Ennever PR, Camidge DR, Doebele RC, Aisner DL. Dramatic Response to Crizotinib in a Patient with Lung Cancer Positive for an HLA-DRB1-MET Gene Fusion. JCO Precis Oncol 2017;2017(1).
    • CDH1
    • 4 Bajrami I, Marlow R, van de Ven M, Brough R, Pemberton HN, Frankum J, Song F, Rafiq R, Konde A, Krastev DB, Menon M, Campbell J, Gulati A, Kumar R, Pettitt SJ, Gurden MD, Cardenosa ML, Chong I, Gazinska P, Wallberg F, Sawyer EJ, Martin LA, Dowsett M, Linardopoulos S, Natrajan R, Ryan CJ, Derksen PWB, Jonkers J, Tutt ANJ, Ashworth A, Lord CJ. E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer. Cancer Discov 2018; 8:498-515.
    • MET
    • 4 Zhu YC, Wang WX, Xu CW, Zhang QX, Du KQ, Chen G, Lv TF, Song Y. Identification of a novel crizotinib-sensitive MET-ATXN7L1 gene fusion variant in lung adenocarcinoma by next generation sequencing. Ann Oncol 2018; 29:2392-2393.
    • 4 Miao YL, Xu QQ. MET Y1003S point mutation shows sensitivity to crizotinib in a patient with lung adenocarcinoma. Lung Cancer 2019; 130:84-86.
    • MET1
    • 4 Liu J, Li X, Peng J. A Novel CAV1-MET Fusion in SCLC Transformation Responds to Crizotinib and Osimertinib Treatment. J Thorac Oncol 2019; 14:e126-e128.
    • MET
    • 4 Wiesweg M, Herold T, Metzenmacher M, Eberhardt WE, Reis H, Darwiche K, Aigner C, Stuschke M, Herrmann K, Nensa F, Schildhaus HU, Schuler M. Clinical response to crizotinib and emergence of resistance in lung adenocarcinoma harboring a MET c-Cbl binding site mutation. Lung Cancer 2020; 139:165-168.
    • 4 Parsons BM, Meier DR, Richmond CS, Gurda GT, Lofgren KA, Burkard ME, Deming DA, Kenny PA. Acquisition of Cabozantinib-Sensitive MET D1228N Mutation During Progression on Crizotinib in MET-Amplified Triple-Negative Breast Cancer. Clin Breast Cancer 2020; 20:e433-e438.
    • ALK
    • 4 Yun MR, Kim DH, Kim SY, Joo HS, Lee YW, Choi HM, Park CW, Heo SG, Kang HN, Lee SS, Schoenfeld AJ, Drilon A, Kang SG, Shim HS, Hong MH, Cui JJ, Kim HR, Cho BC. Repotrectinib Exhibits Potent Antitumor Activity in Treatment-Naïve and Solvent-Front-Mutant ROS1-Rearranged Non-Small Cell Lung Cancer. Clin Cancer Res 2020; 26:3287-3295.
    • ROS1
    • 4 Dong D, Shen G, Da Y, Zhou M, Yang G, Yuan M, Chen R. Successful Treatment of Patients with Refractory High-Grade Serous Ovarian Cancer with GOPC-ROS1 Fusion Using Crizotinib: A Case Report. Oncologist 2020; 25:e1720-e1724.
    • 4 Rodríguez-Antolín C, Rosas-Alonso R, Cruz P, Higuera O, Sánchez-Cabrero D, Esteban-Rodríguez I, Peláez-García A, Fernández Montaño VE, Rodríguez-Jiménez C, Ibáñez de Cáceres I, de Castro J. Novel SLC12A2-ROS1 Fusion in Non-Small Cell Lung Cancer with a Significant Response to Crizotinib: The Importance of Choosing the Appropriate Next-Generation Sequencing Assay. Oncologist 2021; 26:e908-e912.
    • D
    • DB-1303, ARX788
    • ERBB2
    • 4 A Dose-escalation, Expansion Study of ARX788, in Advanced Solid Tumors Subjects With HER2 Expression (ACE-Pan Tumor 01) [NCT03255070]
    • 4 A Study of DB-1303 in Advanced/Metastatic Solid Tumors [NCT05150691]
    • DS-6000a
    • CDH6
    • 4 Hamilton EP, Jauhari S, Moore KN, Rini BI, McLeod R, Lin J, Izumi N, Kundu MG, Myobatake Y, Laadem A, Noguchi Y, Kirui J, Spigel DR. Phase I, two-part, multicenter, first-in-human (FIH) study of DS-6000a in subjects with advanced renal cell carcinoma (RCC) and ovarian tumors (OVC). J Clin Oncol 2022; 40(16_suppl): 3002-3002.
    • DS-6051b
    • NTRK1, NTRK2, NTRK3, ROS1
    • 4 Katayama R, Gong B, Togashi N, Miyamoto M, Kiga M, Iwasaki S, Kamai Y, Tominaga Y, Takeda Y, Kagoshima Y, Shimizu Y, Seto Y, Oh-Hara T, Koike S, Nakao N, Hanzawa H, Watanabe K, Yoda S, Yanagitani N, Hata AN, Shaw AT, Nishio M, Fujita N, Isoyama T. The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models. Nat Commun 2019; 10:3604.
    • DZD9008
    • EGFR
    • 3 Yang JC, Wang M, Mitchell P, Fang J, Nian W, Chiu C, Zhou J, Zhao Y, Su W, Camidge DR, Yang T, Zhu VW, Millward M, Fan Y, Huang WT, Cheng Y, Jiang L, Zheng L, Ye X, Janne PA, Co. P, Ltd , Shanghai , Institute CDC, Boston , MA . Preliminary safety and efficacy results from phase 1 studies of DZD9008 in NSCLC patients with EGFR Exon20 insertion mutations. J Clin Oncol 2021; 39(15_suppl): 9008-9008.
    • Dabrafenib
    • MAP2K2, NRAS
    • R2 Van Allen EM, Wagle N, Sucker A, Treacy DJ, Johannessen CM, Goetz EM, Place CS, Taylor-Weiner A, Whittaker S, Kryukov GV, Hodis E, Rosenberg M, McKenna A, Cibulskis K, Farlow D, Zimmer L, Hillen U, Gutzmer R, Goldinger SM, Ugurel S, Gogas HJ, Egberts F, Berking C, Trefzer U, Loquai C, Weide B, Hassel JC, Gabriel SB, Carter SL, Getz G, Garraway LA, Schadendorf D; Dermatologic Cooperative Oncology Group of Germany (DeCOG). The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov 2014; 4:94-109.
    • MAP2K1+BRAF
    • R2 Carlino MS, Fung C, Shahheydari H, Todd JR, Boyd SC, Irvine M, Nagrial AM, Scolyer RA, Kefford RF, Long GV, Rizos H. Preexisting MEK1P124 mutations diminish response to BRAF inhibitors in metastatic melanoma patients. Clin Cancer Res 2015; 21:98-105.
    • BRAF
    • R2 Yao Z, Yaeger R, Rodrik-Outmezguine VS, Tao A, Torres NM, Chang MT, Drosten M, Zhao H, Cecchi F, Hembrough T, Michels J, Baumert H, Miles L, Campbell NM, de Stanchina E, Solit DB, Barbacid M, Taylor BS, Rosen N. Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS. Nature 2017; 548:234-238.
    • R2 Wang J, Yao Z, Jonsson P, Allen AN, Qin ACR, Uddin S, Dunkel IJ, Petriccione M, Manova K, Haque S, Rosenblum MK, Pisapia DJ, Rosen N, Taylor BS, Pratilas CA. A Secondary Mutation in BRAF Confers Resistance to RAF Inhibition in a BRAFV600E-Mutant Brain Tumor. Cancer Discov 2018; 8:1130-1141.
    • BRAF
    • 1 Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, Rutkowski P, Blank CU, Miller WH Jr, Kaempgen E, Martín-Algarra S, Karaszewska B, Mauch C, Chiarion-Sileni V, Martin AM, Swann S, Haney P, Mirakhur B, Guckert ME, Goodman V, Chapman PB. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2012; 380:358-65.
    • BRAF
    • 2 NCCN Guidelines. https://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf [NCCN:thyroid]
    • 2 Falchook GS, Millward M, Hong D, Naing A, Piha-Paul S, Waguespack SG, Cabanillas ME, Sherman SI, Ma B, Curtis M, Goodman V, Kurzrock R. BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid cancer. Thyroid 2015; 25:71-7.
    • 2 Rothenberg SM, McFadden DG, Palmer EL, Daniels GH, Wirth LJ. Redifferentiation of iodine-refractory BRAF V600E-mutant metastatic papillary thyroid cancer with dabrafenib. Clin Cancer Res 2015; 21:1028-35.
    • BRAF
    • 4 Foster SA, Whalen DM, Özen A, Wongchenko MJ, Yin J, Yen I, Schaefer G, Mayfield JD, Chmielecki J, Stephens PJ, Albacker LA, Yan Y, Song K, Hatzivassiliou G, Eigenbrot C, Yu C, Shaw AS, Manning G, Skelton NJ, Hymowitz SG, Malek S. Activation Mechanism of Oncogenic Deletion Mutations in BRAF, EGFR, and HER2. Cancer Cell 2016; 29:477-493.
    • 4 Identification of targetable BRAF ΔN486_P490 variant by whole-genome sequencing leading to dabrafenib-induced remission of a BRAF-mutant pancreatic adenocarcinoma. Print 2019 Dec. Cold Spring Harb Mol Case Stud 2019; 5(6). pii: a004424.
    • Dabrafenib + Panitumumab
    • KRAS
    • R2 Ahronian LG, Sennott EM, Van Allen EM, Wagle N, Kwak EL, Faris JE, Godfrey JT, Nishimura K, Lynch KD, Mermel CH, Lockerman EL, Kalsy A, Gurski JM Jr, Bahl S, Anderka K, Green LM, Lennon NJ, Huynh TG, Mino-Kenudson M, Getz G, Dias-Santagata D, Iafrate AJ, Engelman JA, Garraway LA, Corcoran RB. Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations. Cancer Discov 2015; 5:358-67.
    • Dabrafenib + Trametinib
    • BRAF
    • 1 Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, Garbe C, Jouary T, Hauschild A, Grob JJ, Chiarion Sileni V, Lebbe C, Mandalà M, Millward M, Arance A, Bondarenko I, Haanen JB, Hansson J, Utikal J, Ferraresi V, Kovalenko N, Mohr P, Probachai V, Schadendorf D, Nathan P, Robert C, Ribas A, DeMarini DJ, Irani JG, Casey M, Ouellet D, Martin AM, Le N, Patel K, Flaherty K. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med 2014; 371:1877-88.
    • BRAF
    • 1B Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY, Schellens JHM, Soria JC, Wen PY, Zielinski C, Cabanillas ME, Urbanowitz G, Mookerjee B, Wang D, Rangwala F, Keam B. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. J Clin Oncol 2018; 36:7-13.
    • MAP2K2, NRAS
    • R2 Van Allen EM, Wagle N, Sucker A, Treacy DJ, Johannessen CM, Goetz EM, Place CS, Taylor-Weiner A, Whittaker S, Kryukov GV, Hodis E, Rosenberg M, McKenna A, Cibulskis K, Farlow D, Zimmer L, Hillen U, Gutzmer R, Goldinger SM, Ugurel S, Gogas HJ, Egberts F, Berking C, Trefzer U, Loquai C, Weide B, Hassel JC, Gabriel SB, Carter SL, Getz G, Garraway LA, Schadendorf D; Dermatologic Cooperative Oncology Group of Germany (DeCOG). The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov 2014; 4:94-109.
    • MAPK1, MAPK3
    • R2 Goetz EM, Ghandi M, Treacy DJ, Wagle N, Garraway LA. ERK mutations confer resistance to mitogen-activated protein kinase pathway inhibitors. Cancer Res 2014; 74:7079-89.
    • MAP2K1
    • R2 Ahronian LG, Sennott EM, Van Allen EM, Wagle N, Kwak EL, Faris JE, Godfrey JT, Nishimura K, Lynch KD, Mermel CH, Lockerman EL, Kalsy A, Gurski JM Jr, Bahl S, Anderka K, Green LM, Lennon NJ, Huynh TG, Mino-Kenudson M, Getz G, Dias-Santagata D, Iafrate AJ, Engelman JA, Garraway LA, Corcoran RB. Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations. Cancer Discov 2015; 5:358-67.
    • BRAF+KRAS, BRAF+MAP2K1, BRAF+NRAS, BRAF+PTEN
    • R2 Facchinetti F, Lacroix L, Mezquita L, Scoazec JY, Loriot Y, Tselikas L, Gazzah A, Rouleau E, Adam J, Michiels S, Massard C, André F, Olaussen KA, Vassal G, Howarth K, Besse B, Soria JC, Friboulet L, Planchard D. Molecular mechanisms of resistance to BRAF and MEK inhibitors in BRAFV600E non-small cell lung cancer. Eur J Cancer 2020; 132:211-223.
    • BRAF
    • 2 Geoerger B, Bouffet E, Whitlock JA, Moertel CL, Hargrave DR, Aerts I, Cohen KJ, Kilburn LB, Wright KD, Choi J, Gasal E, Russo MW, Fox E. Dabrafenib + trametinib combination therapy in pediatric patients with BRAF V600-mutant low-grade glioma: Safety and efficacy results. J Clin Oncol 2020; 38(15_suppl): 10506-10506.
    • 2 Salama AKS, Li S, Macrae ER, Park JI, Mitchell EP, Zwiebel JA, Chen HX, Gray RJ, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Armstrong DK, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Dabrafenib and Trametinib in Patients With Tumors With BRAFV600E Mutations: Results of the NCI-MATCH Trial Subprotocol H. J Clin Oncol 2020; 38:3895-3904.
    • 2 Subbiah V, Lassen U, Élez E, Italiano A, Curigliano G, Javle M, de Braud F, Prager GW, Greil R, Stein A, Fasolo A, Schellens JHM, Wen PY, Viele K, Boran AD, Gasal E, Burgess P, Ilankumaran P, Wainberg ZA. Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial. Lancet Oncol 2020; 21:1234-1243.
    • 2 Wen PY, Stein A, van den Bent M, De Greve J, Wick A, de Vos FYFL, von Bubnoff N, van Linde ME, Lai A, Prager GW, Campone M, Fasolo A, Lopez-Martin JA, Kim TM, Mason WP, Hofheinz RD, Blay JY, Cho DC, Gazzah A, Pouessel D, Yachnin J, Boran A, Burgess P, Ilankumaran P, Gasal E, Subbiah V. Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial. Lancet Oncol 2021 Nov 24. pii: S1470-2045(21)00578-7. [Epub ahead of print]
    • BRAF
    • 3 Geoerger B, Bouffet E, Whitlock JA, Moertel CL, Hargrave DR, Aerts I, Cohen KJ, Kilburn LB, Wright KD, Choi J, Gasal E, Russo MW, Fox E. Dabrafenib + trametinib combination therapy in pediatric patients with BRAF V600-mutant low-grade glioma: Safety and efficacy results. J Clin Oncol 2020; 38(15_suppl): 10506-10506.
    • 3 Hargrave DR, Terashima K, Hara J, Kordes UR, Upadhyaya SA, Sahm F, Bouffet E, Packer RJ, Witt O, Sandalic L, Kieloch A, Russo MW, Cohen KJ. Dabrafenib + trametinib (dab + tram) in relapsed/refractory (r/r) BRAF V600–mutant pediatric high-grade glioma (pHGG): Primary analysis of a phase II trial. J Clin Oncol 2022; 40(16_suppl): 2009-2009.
    • 3 Bouffet E, Hansford J, Garré ML, Hara J, Plant-Fox A, Aerts I, Locatelli F, Lugt JVd, Papusha L, Sahm F, Tabori U, Cohen KJ, Packer RJ, Witt O, Sandalic L, Silva ABPd, Russo MW, Hargrave DR, (KiTZ) CC, (DKFZ) GCRC, Heidelberg aUH, Heidelberg , AG GNP, Basel , Corporation SNP, Hanover E, Trust NGOSHfCNF, Street GO, London , Kingdom U. Primary analysis of a phase II trial of dabrafenib plus trametinib (dab + tram) in BRAF V600–mutant pediatric low-grade glioma (pLGG). J Clin Oncol 2022; 40(17_suppl): LBA2002-LBA2002.
    • 3 Corcoran RB, Atreya CE, Falchook GS, Kwak EL, Ryan DP, Bendell JC, Hamid O, Messersmith WA, Daud A, Kurzrock R, Pierobon M, Sun P, Cunningham E, Little S, Orford K, Motwani M, Bai Y, Patel K, Venook AP, Kopetz S. Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer. J Clin Oncol 2015; 33:4023-31.
    • BRAF
    • 4 Guan M, Bender RJ, Pishvaian MJ, Halverson DC, Tuli R, Klempner SJ, Wainberg ZA, Singhi AD, Petricoin E, Hendifar AE. Molecular and clinical characterization of BRAF mutations in pancreatic ductal adenocarcinomas (PDACs). J Clin Oncol 2018; 36(4_suppl): 214-214.
    • 4 Burkart J, Owen D, Shah MH, Abdel-Misih SRZ, Roychowdhury S, Wesolowski R, Haraldsdottir S, Reeser JW, Samorodnitsky E, Smith A, Konda B. Targeting BRAF Mutations in High-Grade Neuroendocrine Carcinoma of the Colon. J Natl Compr Canc Netw 2018; 16:1035-1040.
    • 4 Hendifar A, Blais EM, Wolpin B, Subbiah V, Collisson E, Singh I, Cannon T, Shaw K, Petricoin EF 3rd, Klempner S, Lyons E, Wang-Gillam A, Pishvaian MJ, O'Reilly EM. Retrospective Case Series Analysis of RAF Family Alterations in Pancreatic Cancer: Real-World Outcomes From Targeted and Standard Therapies. JCO Precis Oncol 2021; 5. pii: PO.20.00494. eCollection 2021.
    • Dabrafenib + Trametinib + Osimertinib
    • EGFR+BRAF
    • 4 Ribeiro MFSA, Knebel FH, Bettoni F, Saddi R, Sacardo KP, Canedo FSNA, Alessi JVM, Shimada AK, Marin JFG, Camargo AA, Katz A. Impressive response to dabrafenib, trametinib, and osimertinib in a metastatic EGFR-mutant/BRAF V600E lung adenocarcinoma patient. NPJ Precis Oncol 2021; 5:5.
    • Dacomitinib
    • EGFR
    • R1 Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong KK, Meyerson M, Eck MJ. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A 2008; 105:2070-5.
    • R1 Yasuda H, Kobayashi S, Costa DB. EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications. Lancet Oncol 2012; 13:e23-31.
    • EGFR
    • R2 Chi AS, Cahill DP, Reardon DA, Wen PY, Mikkelsen T, Peereboom DM, Wong ET, Gerstner ER, Dietrich J, Plotkin SR, Norden AD, Lee EQ, Nayak L, Tanaka S, Wakimoto H, Lelic N, Koerner MV, Klofas LK, Bertalan MS, Arrillaga-Romany IC, Betensky RA, Curry WT, Borger DR, Balaj L, Kitchen RR, Chakrabortty SK, Valentino MD, Skog J, Breakefield XO, Iafrate AJ, Batchelor TT. Exploring Predictors of Response to Dacomitinib in EGFR-Amplified Recurrent Glioblastoma. JCO Prec Oncol 2019; 10.1200/PO.19.00295 4 593-613. Published online June 8, 2020.
    • R2 Yasuda H, Park E, Yun CH, Sng NJ, Lucena-Araujo AR, Yeo WL, Huberman MS, Cohen DW, Nakayama S, Ishioka K, Yamaguchi N, Hanna M, Oxnard GR, Lathan CS, Moran T, Sequist LV, Chaft JE, Riely GJ, Arcila ME, Soo RA, Meyerson M, Eck MJ, Kobayashi SS, Costa DB. Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer. Sci Transl Med 2013; 5:216ra177.
    • R2 Matsushima S, Ohtsuka K, Ohnishi H, Fujiwara M, Nakamura H, Morii T, Kishino T, Goto H, Watanabe T. V843I, a lung cancer predisposing EGFR mutation, is responsible for resistance to EGFR tyrosine kinase inhibitors. J Thorac Oncol 2014; 9:1377-84.
    • ERBB2
    • R2 Kris MG, Camidge DR, Giaccone G, Hida T, Li BT, O'Connell J, Taylor I, Zhang H, Arcila ME, Goldberg Z, Jänne PA. Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumors. Ann Oncol 2015; 26:1421-7.
    • EGFR
    • R2 Sepúlveda-Sánchez JM, Vaz MÁ, Balañá C, Gil-Gil M, Reynés G, Gallego Ó, Martínez-García M, Vicente E, Quindós M, Luque R, Ramos A, Ruano Y, Pérez-Segura P, Benavides M, Sánchez-Gómez P, Hernández-Laín A. Phase II trial of dacomitinib, a pan-human EGFR tyrosine kinase inhibitor, in recurrent glioblastoma patients with EGFR amplification. Neuro Oncol 2017; 19:1522-1531.
    • R2 Kobayashi Y, Fujino T, Nishino M, Koga T, Chiba M, Sesumi Y, Ohara S, Shimoji M, Tomizawa K, Takemoto T, Mitsudomi T. EGFR T790M and C797S Mutations as Mechanisms of Acquired Resistance to Dacomitinib. J Thorac Oncol 2018; 13:727-731.
    • MET
    • R2 Lai GGY, Lim TH, Lim J, Liew PJR, Kwang XL, Nahar R, Aung ZW, Takano A, Lee YY, Lau DPX, Tan GS, Tan SH, Tan WL, Ang MK, Toh CK, Tan BS, Devanand A, Too CW, Gogna A, Ong BH, Koh TPT, Kanesvaran R, Ng QS, Jain A, Rajasekaran T, Yuan J, Lim TKH, Lim AST, Hillmer AM, Lim WT, Iyer NG, Tam WL, Zhai W, Tan EH, Tan DSW. Clonal MET Amplification as a Determinant of Tyrosine Kinase Inhibitor Resistance in Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer. J Clin Oncol 2019; 37:876-884.
    • ERBB2
    • R2 Robichaux JP, Elamin YY, Vijayan RSK, Nilsson MB, Hu L, He J, Zhang F, Pisegna M, Poteete A, Sun H, Li S, Chen T, Han H, Negrao MV, Ahnert JR, Diao L, Wang J, Le X, Meric-Bernstam F, Routbort M, Roeck B, Yang Z, Raymond VM, Lanman RB, Frampton GM, Miller VA, Schrock AB, Albacker LA, Wong KK, Cross JB, Heymach JV. Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 Activity. Cancer Cell 2019; 36:444-457.e7.
    • EGFR
    • R2 Zhu C, Zhuang W, Chen L, Yang W, Ou WB. Frontiers of ctDNA, targeted therapies, and immunotherapy in non-small-cell lung cancer. Transl Lung Cancer Res 2020; 9:111-138.
    • R2 Lee C, Kim M, Kim DW, Kim TM, Kim S, Im SW, Jeon YK, Keam B, Ku JL, Heo DS. Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non-Small Cell Lung Cancer. Cancer Res Treat 2021 May 3. [Epub ahead of print]
    • R2 Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 2021; 597:732-737.
    • EGFR
    • 2 Ramalingam SS, Jänne PA, Mok T, O'Byrne K, Boyer MJ, Von Pawel J, Pluzanski A, Shtivelband M, Docampo LI, Bennouna J, Zhang H, Liang JQ, Doherty JP, Taylor I, Mather CB, Goldberg Z, O'Connell J, Paz-Ares L. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol 2014; 15:1369-78.
    • 2 Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Nadanaciva S, Sandin R, Mok TS. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol 2017; 18:1454-1466.
    • ERBB2
    • 3 Kris MG, Camidge DR, Giaccone G, Hida T, Li BT, O'Connell J, Taylor I, Zhang H, Arcila ME, Goldberg Z, Jänne PA. Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumors. Ann Oncol 2015; 26:1421-7.
    • 3 Zhao S, Fang W, Pan H, Yang Y, Liang Y, Yang L, Dong X, Zhan J, Wang K, Zhang L. Conformational Landscapes of HER2 Exon 20 Insertions Explain Their Sensitivity to Kinase Inhibitors in Lung Adenocarcinoma. J Thorac Oncol 2020; 15:962-972.
    • EGFR
    • 4 Chi AS, Cahill DP, Reardon DA, Wen PY, Mikkelsen T, Peereboom DM, Wong ET, Gerstner ER, Dietrich J, Plotkin SR, Norden AD, Lee EQ, Nayak L, Tanaka S, Wakimoto H, Lelic N, Koerner MV, Klofas LK, Bertalan MS, Arrillaga-Romany IC, Betensky RA, Curry WT, Borger DR, Balaj L, Kitchen RR, Chakrabortty SK, Valentino MD, Skog J, Breakefield XO, Iafrate AJ, Batchelor TT. Exploring Predictors of Response to Dacomitinib in EGFR-Amplified Recurrent Glioblastoma. JCO Prec Oncol 2019; 10.1200/PO.19.00295 4 593-613. Published online June 8, 2020.
    • 4 Necchi A, Lo Vullo S, Perrone F, Raggi D, Giannatempo P, Calareso G, Nicolai N, Piva L, Biasoni D, Catanzaro M, Torelli T, Stagni S, Togliardi E, Colecchia M, Busico A, Gloghini A, Testi A, Mariani L, Salvioni R. First-line therapy with dacomitinib, an orally available pan-HER tyrosine kinase inhibitor, for locally advanced or metastatic penile squamous cell carcinoma: results of an open-label, single-arm, single-centre, phase 2 study. BJU Int 2018; 121:348-356.
    • ERBB2
    • 4 Robichaux JP, Elamin YY, Vijayan RSK, Nilsson MB, Hu L, He J, Zhang F, Pisegna M, Poteete A, Sun H, Li S, Chen T, Han H, Negrao MV, Ahnert JR, Diao L, Wang J, Le X, Meric-Bernstam F, Routbort M, Roeck B, Yang Z, Raymond VM, Lanman RB, Frampton GM, Miller VA, Schrock AB, Albacker LA, Wong KK, Cross JB, Heymach JV. Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 Activity. Cancer Cell 2019; 36:444-457.e7.
    • EGFR
    • 4 Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 2021; 597:732-737.
    • Daratumumab + Bortezomib + Dexamethasone
    • CD38
    • 1 Nijhof IS, Casneuf T, van Velzen J, van Kessel B, Axel AE, Syed K, Groen RW, van Duin M, Sonneveld P, Minnema MC, Zweegman S, Chiu C, Bloem AC, Mutis T, Lokhorst HM, Sasser AK, van de Donk NW. CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. Blood 2016; 128:959-70.
    • 1 Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, Spicka I, Hungria V, Munder M, Mateos MV, Mark TM, Qi M, Schecter J, Amin H, Qin X, Deraedt W, Ahmadi T, Spencer A, Sonneveld P; CASTOR Investigators. Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med 2016; 375:754-66.
    • Daratumumab + Hyaluronidase-fihj
    • CD38
    • 2 Mateos MV, Nahi H, Legiec W, Grosicki S, Vorobyev V, Spicka I, Hungria V, Korenkova S, Bahlis N, Flogegard M, Bladé J, Moreau P, Kaiser M, Iida S, Laubach J, Magen H, Cavo M, Hulin C, White D, De Stefano V, Clemens PL, Masterson T, Lantz K, O'Rourke L, Heuck C, Qin X, Parasrampuria DA, Yuan Z, Xu S, Qi M, Usmani SZ. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial. Lancet Haematol 2020; 7:e370-e380.
    • Daratumumab + Lenalidomide + Dexamethasone
    • CD38
    • 1B Nijhof IS, Casneuf T, van Velzen J, van Kessel B, Axel AE, Syed K, Groen RW, van Duin M, Sonneveld P, Minnema MC, Zweegman S, Chiu C, Bloem AC, Mutis T, Lokhorst HM, Sasser AK, van de Donk NW. CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. Blood 2016; 128:959-70.
    • 1B Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, Plesner T, Yoon SS, Ben Yehuda D, Richardson PG, Goldschmidt H, Reece D, Lisby S, Khokhar NZ, O'Rourke L, Chiu C, Qin X, Guckert M, Ahmadi T, Moreau P; POLLUX Investigators. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med 2016; 375:1319-1331.
    • Dasatinib
    • ABL1
    • R1 Talpaz M, Shah NP, Kantarjian H, Donato N, Nicoll J, Paquette R, Cortes J, O'Brien S, Nicaise C, Bleickardt E, Blackwood-Chirchir MA, Iyer V, Chen TT, Huang F, Decillis AP, Sawyers CL. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 2006; 354:2531-41.
    • R1 Redaelli S, Piazza R, Rostagno R, Magistroni V, Perini P, Marega M, Gambacorti-Passerini C, Boschelli F. Activity of bosutinib, dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants. J Clin Oncol 2009; 27:469-71.
    • R1 Jiang Q, Qin YZ, Lai YY, Jiang H, Wang J, Huang XJ. Patients with Philadelphia-positive leukemia with Y253H or F359V mutation have a high risk of developing new mutations in the setting of dasatinib resistance. Leuk Lymphoma 2015; 56:2075-81.
    • BAP1, NF1, PTPN11, WT1
    • R2 Bigenzahn JW, Collu GM, Kartnig F, Pieraks M, Vladimer GI, Heinz LX, Sedlyarov V, Schischlik F, Fauster A, Rebsamen M, Parapatics K, Blomen VA, Müller AC, Winter GE, Kralovics R, Brummelkamp TR, Mlodzik M, Superti-Furga G. LZTR1 is a regulator of RAS ubiquitination and signaling. Science 2018; 362:1171-1177.
    • ABL1
    • 1 Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, Moiraghi B, Shen Z, Mayer J, Pasquini R, Nakamae H, Huguet F, Boqué C, Chuah C, Bleickardt E, Bradley-Garelik MB, Zhu C, Szatrowski T, Shapiro D, Baccarani M. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010; 362:2260-70.
    • ABL1
    • 2 Talpaz M, Shah NP, Kantarjian H, Donato N, Nicoll J, Paquette R, Cortes J, O'Brien S, Nicaise C, Bleickardt E, Blackwood-Chirchir MA, Iyer V, Chen TT, Huang F, Decillis AP, Sawyers CL. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 2006; 354:2531-41.
    • 2 Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, Moiraghi B, Shen Z, Mayer J, Pasquini R, Nakamae H, Huguet F, Boqué C, Chuah C, Bleickardt E, Bradley-Garelik MB, Zhu C, Szatrowski T, Shapiro D, Baccarani M. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010; 362:2260-70.
    • PDGFRA
    • 2 Schuetze SM, Bolejack V, Thomas DG, von Mehren M, Patel S, Samuels B, Choy E, D'Amato G, Staddon AP, Ganjoo KN, Chow WA, Rushing DA, Forscher CA, Priebat DA, Loeb DM, Chugh R, Okuno S, Reinke DK, Baker LH. Association of Dasatinib With Progression-Free Survival Among Patients With Advanced Gastrointestinal Stromal Tumors Resistant to Imatinib. JAMA Oncol 2018; 4:814-820.
    • ARID1A
    • 4 Miller RE, Brough R, Bajrami I, Williamson CT, McDade S, Campbell J, Kigozi A, Rafiq R, Pemberton H, Natrajan R, Joel J, Astley H, Mahoney C, Moore JD, Torrance C, Gordan JD, Webber JT, Levin RS, Shokat KM, Bandyopadhyay S, Lord CJ, Ashworth A. Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib. Mol Cancer Ther 2016; 15:1472-84.
    • Dasatinib + Blinatumomab
    • ABL1
    • 2 Foà R, Bassan R, Vitale A, Elia L, Piciocchi A, Puzzolo MC, Canichella M, Viero P, Ferrara F, Lunghi M, Fabbiano F, Bonifacio M, Fracchiolla N, Di Bartolomeo P, Mancino A, De Propris MS, Vignetti M, Guarini A, Rambaldi A, Chiaretti S; GIMEMA Investigators. Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults. N Engl J Med 2020; 383:1613-1623.
    • Debio1347
    • FGFR3
    • R2 Chell V, Balmanno K, Little AS, Wilson M, Andrews S, Blockley L, Hampson M, Gavine PR, Cook SJ. Tumour cell responses to new fibroblast growth factor receptor tyrosine kinase inhibitors and identification of a gatekeeper mutation in FGFR3 as a mechanism of acquired resistance. Oncogene 2013; 32:3059-70.
    • FGFR2
    • R2 Byron SA, Chen H, Wortmann A, Loch D, Gartside MG, Dehkhoda F, Blais SP, Neubert TA, Mohammadi M, Pollock PM. The N550K/H mutations in FGFR2 confer differential resistance to PD173074, dovitinib, and ponatinib ATP-competitive inhibitors. Neoplasia 2013; 15:975-88.
    • R2 Helsten T, Schwaederle M, Kurzrock R. Fibroblast growth factor receptor signaling in hereditary and neoplastic disease: biologic and clinical implications. Cancer Metastasis Rev 2015; 34:479-96.
    • FGFR1
    • R2 Cowell JK, Qin H, Hu T, Wu Q, Bhole A, Ren M. Mutation in the FGFR1 tyrosine kinase domain or inactivation of PTEN is associated with acquired resistance to FGFR inhibitors in FGFR1-driven leukemia/lymphomas. Int J Cancer 2017; 141:1822-1829.
    • FGFR3
    • R2 Pal SK, Rosenberg JE, Hoffman-Censits JH, Berger R, Quinn DI, Galsky MD, Wolf J, Dittrich C, Keam B, Delord JP, Schellens JHM, Gravis G, Medioni J, Maroto P, Sriuranpong V, Charoentum C, Burris HA, Grünwald V, Petrylak D, Vaishampayan U, Gez E, De Giorgi U, Lee JL, Voortman J, Gupta S, Sharma S, Mortazavi A, Vaughn DJ, Isaacs R, Parker K, Chen X, Yu K, Porter D, Graus Porta D, Bajorin DF. Efficacy of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Inhibitor, in Patients with Previously Treated Advanced Urothelial Carcinoma with FGFR3 Alterations. Cancer Discov 2018; 8:812-821.
    • FGFR1
    • 4 Cleary JM, Iyer G, Oh D, Mellinghoff IK, Goyal L, Ng MC, Meric-Bernstam F, Matos I, Chao T, Sarkouh RA, Cretegny K, Nicolas-Metral V, Pokorska-Bocci A, Vaslin A, Zanna C, Zubel A, Tabernero J, Flaherty K, Hyman DM. Final results from the phase I study expansion cohort of the selective FGFR inhibitor Debio 1,347 in patients with solid tumors harboring an FGFR gene fusion. J Clin Oncol 2020; 38(15_suppl): 3603-3603.
    • FGFR1, FGFR2, FGFR3
    • 4 Debio 1347-101 Phase I Trial in Advanced Solid Tumours With Fibroblast Growth Factor Receptor (FGFR) Alterations [NCT01948297]
    • Defactinib
    • NF2
    • R2 Jackman DM, Jegede O, Zauderer MG, Mitchell EP, Zwiebel J, Gray RJ, Li S, McShane L, Rubinstein L, Patton DR, Williams PM, Hamilton SR, Conley BA, Arteaga CL, Harris L, O'Dwyer PJ, Chen AP, Flaherty K, Nashville , Program TCD, Institute NC, Rockville , Pennsylvania MUo, Hospital P, Philadelphia , Program PDTCCTD, Diagnosis DoCTa, Institute NC, Bethesda , Hospital MDCIMSG, Boston , MA . A phase 2 study of defactinib (VS-6063) in patients with NF2 altered tumors: Results from NCI-match (EAY131) subprotocol U. J Clin Oncol 2021; 39(15_suppl): 3087-3087.
    • Depatuxizumab mafodotin
    • EGFR
    • R2 Van Den Bent M, Eoli M, Sepulveda JM, Smits M, Walenkamp A, Frenel JS, Franceschi E, Clement PM, Chinot O, De Vos F, Whenham N, Sanghera P, Weller M, Dubbink HJ, French P, Looman J, Dey J, Krause S, Ansell P, Nuyens S, Spruyt M, Brilhante J, Coens C, Gorlia T, Golfinopoulos V. INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma. Neuro Oncol 2020; 22:684-693.
    • EGFR
    • 4 van den Bent M, Gan HK, Lassman AB, Kumthekar P, Merrell R, Butowski N, Lwin Z, Mikkelsen T, Nabors LB, Papadopoulos KP, Penas-Prado M, Simes J, Wheeler H, Walbert T, Scott AM, Gomez E, Lee HJ, Roberts-Rapp L, Xiong H, Bain E, Ansell PJ, Holen KD, Maag D, Reardon DA. Efficacy of depatuxizumab mafodotin (ABT-414) monotherapy in patients with EGFR-amplified, recurrent glioblastoma: results from a multi-center, international study. Cancer Chemother Pharmacol 2017; 80:1209-1217.
    • Dinaciclib
    • MCL1
    • 4 Booher RN, Hatch H, Dolinski BM, Nguyen T, Harmonay L, Al-Assaad AS, Ayers M, Nebozhyn M, Loboda A, Hirsch HA, Zhang T, Shi B, Merkel CE, Angagaw MH, Wang Y, Long BJ, Lennon XQ, Miselis N, Pucci V, Monahan JW, Lee J, Kondic AG, Im EK, Mauro D, Blanchard R, Gilliland G, Fawell SE, Zawel L, Schuller AG, Strack P. MCL1 and BCL-xL levels in solid tumors are predictive of dinaciclib-induced apoptosis. PLoS One 2014; 9:e108371. eCollection 2014.
    • Dinaciclib + MK2206
    • CCNE1
    • 4 Au-Yeung G, Lang F, Azar WJ, Mitchell C, Jarman KE, Lackovic K, Aziz D, Cullinane C, Pearson RB, Mileshkin L, Rischin D, Karst AM, Drapkin R, Etemadmoghadam D, Bowtell DD. Selective Targeting of Cyclin E1-Amplified High-Grade Serous Ovarian Cancer by Cyclin-Dependent Kinase 2 and AKT Inhibition. Clin Cancer Res 2017; 23:1862-1874.
    • Docetaxel + Trastuzumab
    • ERBB2
    • 1 Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Antón A, Lluch A, Kennedy J, O'Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol 2005; 23:4265-74.
    • Dostarlimab
    • Microsatellite Instability, Mismatch repair
    • 2 Oaknin A, Tinker AV, Gilbert L, Samouëlian V, Mathews C, Brown J, Barretina-Ginesta MP, Moreno V, Gravina A, Abdeddaim C, Banerjee S, Guo W, Danaee H, Im E, Sabatier R. Clinical Activity and Safety of the Anti-Programmed Death 1 Monoclonal Antibody Dostarlimab for Patients With Recurrent or Advanced Mismatch Repair-Deficient Endometrial Cancer: A Nonrandomized Phase 1 Clinical Trial. JAMA Oncol 2020 Oct 1. [Epub ahead of print]
    • Mismatch repair
    • 3 Andre T, Berton D, Curigliano G, Ellard S, Pérez JMT, Arkenau H, Abdeddaim C, Moreno V, Guo W, Im E, Starling N. Safety and efficacy of anti–PD-1 antibody dostarlimab in patients (pts) with mismatch repair-deficient (dMMR) solid cancers: Results from GARNET study. J Clin Oncol 2021; 39(3_suppl): 9-9.
    • Dovitinib
    • FGFR2
    • R2 Byron SA, Chen H, Wortmann A, Loch D, Gartside MG, Dehkhoda F, Blais SP, Neubert TA, Mohammadi M, Pollock PM. The N550K/H mutations in FGFR2 confer differential resistance to PD173074, dovitinib, and ponatinib ATP-competitive inhibitors. Neoplasia 2013; 15:975-88.
    • R2 Helsten T, Schwaederle M, Kurzrock R. Fibroblast growth factor receptor signaling in hereditary and neoplastic disease: biologic and clinical implications. Cancer Metastasis Rev 2015; 34:479-96.
    • FGFR1
    • R2 Yoza K, Himeno R, Amano S, Kobashigawa Y, Amemiya S, Fukuda N, Kumeta H, Morioka H, Inagaki F. Biophysical characterization of drug-resistant mutants of fibroblast growth factor receptor 1. Genes Cells 2016; 21:1049-1058.
    • FGFR2
    • 4 Konecny GE, Finkler N, Garcia AA, Lorusso D, Lee PS, Rocconi RP, Fong PC, Squires M, Mishra K, Upalawanna A, Wang Y, Kristeleit R. Second-line dovitinib (TKI258) in patients with FGFR2-mutated or FGFR2-non-mutated advanced or metastatic endometrial cancer: a non-randomised, open-label, two-group, two-stage, phase 2 study. Lancet Oncol 2015; 16:686-94.
    • Duligotuzumab + FOLFIRI
    • KRAS+NRAS
    • R2 Hill AG, Findlay MP, Burge ME, Jackson C, Alfonso PG, Samuel L, Ganju V, Karthaus M, Amatu A, Jeffery M, Bartolomeo MD, Bridgewater J, Coveler AL, Hidalgo M, Kapp AV, Sufan RI, McCall BB, Hanley WD, Penuel EM, Pirzkall A, Tabernero J. Phase II Study of the Dual EGFR/HER3 Inhibitor Duligotuzumab (MEHD7945A) versus Cetuximab in Combination with FOLFIRI in Second-Line RAS Wild-Type Metastatic Colorectal Cancer. Clin Cancer Res 2018; 24:2276-2284.
    • Durvalumab
    • CD274
    • 3 Powles T, O'Donnell PH, Massard C, Arkenau HT, Friedlander TW, Hoimes CJ, Lee JL, Ong M, Sridhar SS, Vogelzang NJ, Fishman MN, Zhang J, Srinivas S, Parikh J, Antal J, Jin X, Gupta AK, Ben Y, Hahn NM. Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study. JAMA Oncol 2017; 3:e172411.
    • ARID1A, ARID1B, PBRM1, SMARCA4, SMARCB1
    • 4 Botta GP, Kato S, Patel H, Fanta P, Lee S, Okamura R, Kurzrock R. SWI/SNF complex alterations as a biomarker of immunotherapy efficacy in pancreatic cancer. JCI Insight 2021; 6(18). pii: e150453.
    • CDK12
    • 4 Pan E, Cabal A, Javier-DesLoges J, Patel D, Panian J, Lee S, Shaya J, Nonato T, Xu X, Stewart T, Rose B, Shabaik A, Cohen E, Kurzrock R, Tamayo P, McKay RR. Analysis of CDK12 alterations in a pan-cancer database. Cancer Med 2022; 11:753-763.
    • Durvalumab + Olaparib
    • BRCA1
    • 3 Domchek SM, Postel-Vinay S, Im SA, Park YH, Delord JP, Italiano A, Alexandre J, You B, Bastian S, Krebs MG, Wang D, Waqar SN, Lanasa M, Rhee J, Gao H, Rocher-Ros V, Jones EV, Gulati S, Coenen-Stass A, Kozarewa I, Lai Z, Angell HK, Opincar L, Herbolsheimer P, Kaufman B. Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Lancet Oncol 2020; 21:1155-1164.
    • ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, RAD51C
    • 4 Rosenberg JE, Park SH, Kozlov V, Dao TV, Castellano D, Li JR, Mukherjee SD, Howells K, Dry H, Lanasa MC, Stewart R, Bajorin DF. Durvalumab Plus Olaparib in Previously Untreated, Platinum-Ineligible Patients With Metastatic Urothelial Carcinoma: A Multicenter, Randomized, Phase II Trial (BAYOU). J Clin Oncol 2022 Jun 23:JCO2200205. [Epub ahead of print]
    • Durvalumab + Paclitaxel + Trastuzumab deruxtecan
    • ERBB2
    • 4 Schmid P, Im S, Armstrong A, Park YH, Chung W, Nowecki Z, Lord S, Wysocki PJ, Lu Y, Dry H, Karwe V, Stewart R, Herbolsheimer P, Nunes AT, Jung KH, Ulsan Uo, Seoul , Korea S. BEGONIA: Phase 1b/2 study of durvalumab (D) combinations in locally advanced/metastatic triple-negative breast cancer (TNBC)—Initial results from arm 1, d+paclitaxel (P), and arm 6, d+trastuzumab deruxtecan (T-DXd). J Clin Oncol 2021; 39(15_suppl): 1023-1023.
    • Durvalumab + Savolitinib
    • HGF, MET
    • 3 Rodriguez CS, Larkin J, Patel PM, Valderrama BP, Rodriguez-Vida A, Glen H, Thistlethwaite F, Ralph C, Srinivasan G, Mendez-Vidal MJ, Carter A, Tyson C, Prendergast A, Mousa K, Powles T. Clinical activity of durvalumab and savolitinib in MET-driven, metastatic papillary renal cancer. J Clin Oncol 2021; 39(15_suppl): 4511-4511.
    • Durvalumab + Tremelimumab
    • Tumour Mutational Burden
    • 3 Rizvi NA, Cho BC, Reinmuth N, Lee KH, Luft A, Ahn MJ, van den Heuvel MM, Cobo M, Vicente D, Smolin A, Moiseyenko V, Antonia SJ, Le Moulec S, Robinet G, Natale R, Schneider J, Shepherd FA, Geater SL, Garon EB, Kim ES, Goldberg SB, Nakagawa K, Raja R, Higgs BW, Boothman AM, Zhao L, Scheuring U, Stockman PK, Chand VK, Peters S; MYSTIC Investigators. Durvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non-Small Cell Lung Cancer: The MYSTIC Phase 3 Randomized Clinical Trial. JAMA Oncol 2020 Apr 9. [Epub ahead of print]
    • Tumour Mutational Burden+Microsatellite, Tumour Mutational Burden+Mismatch repair
    • 4 Chen EX, Jonker DJ, Loree JM, Kennecke HF, Berry SR, Couture F, Ahmad CE, Goffin JR, Kavan P, Harb M, Colwell B, Samimi S, Samson B, Abbas T, Aucoin N, Aubin F, Koski SL, Wei AC, Magoski NM, Tu D, O'Callaghan CJ. Effect of Combined Immune Checkpoint Inhibition vs Best Supportive Care Alone in Patients With Advanced Colorectal Cancer: The Canadian Cancer Trials Group CO.26 Study. JAMA Oncol 2020; 6:831-838.
    • CDK12
    • 4 Schweizer MT, Ha G, Gulati R, Brown LC, McKay RR, Dorff T, Hoge ACH, Reichel J, Vats P, Kilari D, Patel V, Oh WK, Chinnaiyan A, Pritchard CC, Armstrong AJ, Montgomery RB, Alva A. CDK12-Mutated Prostate Cancer: Clinical Outcomes With Standard Therapies and Immune Checkpoint Blockade. JCO Precis Oncol 2020;4:382-392.
    • E
    • E-EDV-D682
    • EGFR
    • 4 Lundy J, Marx GM, MacDiarmid J, Brahmbhatt H, Ganju V. Interim data: Phase I/IIa study of EGFR-targeted EDV nanocells carrying cytotoxic drug PNU-159682 (E-EDV-D682) with immunomodulatory adjuvant EDVs carrying α-galactosyl ceramide (EDV-GC) in patients with recurrent, metastatic pancreatic cancer. J Clin Oncol 2020; 38(15_suppl): 4632-4632.
    • EGFR inhibitor
    • BRAF+EGFR
    • R2 Vojnic M, Kubota D, Kurzatkowski C, Offin M, Suzawa K, Benayed R, Schoenfeld AJ, Plodkowski AJ, Poirier JT, Rudin CM, Kris MG, Rosen NX, Yu HA, Riely GJ, Arcila ME, Somwar R, Ladanyi M. Acquired BRAF Rearrangements Induce Secondary Resistance to EGFR therapy in EGFR-Mutated Lung Cancers. J Thorac Oncol 2019; 14:802-815.
    • EGFR inhibitor,exon 20 selective
    • EGFR
    • 4 Vyse S, Huang PH. Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer. Signal Transduct Target Ther 2019; 4:5. eCollection 2019.
    • EPZ011989
    • BAP1
    • 4 LaFave LM, Béguelin W, Koche R, Teater M, Spitzer B, Chramiec A, Papalexi E, Keller MD, Hricik T, Konstantinoff K, Micol JB, Durham B, Knutson SK, Campbell JE, Blum G, Shi X, Doud EH, Krivtsov AV, Chung YR, Khodos I, de Stanchina E, Ouerfelli O, Adusumilli PS, Thomas PM, Kelleher NL, Luo M, Keilhack H, Abdel-Wahab O, Melnick A, Armstrong SA, Levine RL. Loss of BAP1 function leads to EZH2-dependent transformation. Nat Med 2015; 21:1344-9.
    • EPZ6438
    • H3F3A
    • 4 Mohammad F, Weissmann S, Leblanc B, Pandey DP, Højfeldt JW, Comet I, Zheng C, Johansen JV, Rapin N, Porse BT, Tvardovskiy A, Jensen ON, Olaciregui NG, Lavarino C, Suñol M, de Torres C, Mora J, Carcaboso AM, Helin K. EZH2 is a potential therapeutic target for H3K27M-mutant pediatric gliomas. Nat Med 2017; 23:483-492.
    • ERBB2 inhibitor
    • ERBB2
    • 4 Robichaux JP, Elamin YY, Vijayan RSK, Nilsson MB, Hu L, He J, Zhang F, Pisegna M, Poteete A, Sun H, Li S, Chen T, Han H, Negrao MV, Ahnert JR, Diao L, Wang J, Le X, Meric-Bernstam F, Routbort M, Roeck B, Yang Z, Raymond VM, Lanman RB, Frampton GM, Miller VA, Schrock AB, Albacker LA, Wong KK, Cross JB, Heymach JV. Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 Activity. Cancer Cell 2019; 36:444-457.e7.
    • ERK inhibitor
    • MAP2K1
    • 4 Smalley I, Smalley KSM. ERK Inhibition: A New Front in the War against MAPK Pathway-Driven Cancers? Cancer Discov 2018; 8:140-142.
    • ETC-159
    • RNF43
    • 4 Yu J, Yusoff PAM, Woutersen DTJ, Goh P, Harmston N, Smits R, Epstein DM, Virshup DM, Madan B. The Functional Landscape of Patient-Derived RNF43 Mutations Predicts Sensitivity to Wnt Inhibition. Cancer Res 2020; 80:5619-5632.
    • Elacestrant
    • ERBB2+ESR1, ESR1
    • 2 Bidard FC, Kaklamani VG, Neven P, Streich G, Montero AJ, Forget F, Mouret-Reynier MA, Sohn JH, Taylor D, Harnden KK, Khong H, Kocsis J, Dalenc F, Dillon PM, Babu S, Waters S, Deleu I, García Sáenz JA, Bria E, Cazzaniga M, Lu J, Aftimos P, Cortés J, Liu S, Tonini G, Laurent D, Habboubi N, Conlan MG, Bardia A. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol 2022 May 18:JCO2200338. [Epub ahead of print]
    • ESR1
    • 3 Bardia A, Kaklamani V, Wilks S, Weise A, Richards D, Harb W, Osborne C, Wesolowski R, Karuturi M, Conkling P, Bagley RG, Wang Y, Conlan MG, Kabos P. Phase I Study of Elacestrant (RAD1901), a Novel Selective Estrogen Receptor Degrader, in ER-Positive, HER2-Negative Advanced Breast Cancer. J Clin Oncol 2021 Jan 29:JCO2002272. [Epub ahead of print]
    • ESR1
    • 4 Kingston B, Pearson A, Herrera-Abreu MT, Cutts R, Moretti L, Kilburn L, Johnson H, MacPherson IR, Ring AE, Bliss J, Katzenellenbogen JA, Turner NC. ESR1 F404 mutations and acquired resistance to fulvestrant in the plasmaMATCH study. J Clin Oncol 2022; 40(16_suppl): 1009-1009.
    • 4 Bardia A, Kaklamani V, Wilks S, Weise A, Richards D, Harb W, Osborne C, Wesolowski R, Karuturi M, Conkling P, Bagley RG, Wang Y, Conlan MG, Kabos P. Phase I Study of Elacestrant (RAD1901), a Novel Selective Estrogen Receptor Degrader, in ER-Positive, HER2-Negative Advanced Breast Cancer. J Clin Oncol 2021 Jan 29:JCO2002272. [Epub ahead of print]
    • Elotuzumab + Lenalidomide + Dexamethasone
    • SLAMF7
    • 1B Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, Walter-Croneck A, Moreau P, Mateos MV, Magen H, Belch A, Reece D, Beksac M, Spencer A, Oakervee H, Orlowski RZ, Taniwaki M, Röllig C, Einsele H, Wu KL, Singhal A, San-Miguel J, Matsumoto M, Katz J, Bleickardt E, Poulart V, Anderson KC, Richardson P; ELOQUENT-2 Investigators. Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. N Engl J Med 2015; 373:621-31.
    • Emactuzumab
    • CSF1
    • 3 Cassier PA, Italiano A, Gomez-Roca CA, Le Tourneau C, Toulmonde M, Cannarile MA, Ries C, Brillouet A, Müller C, Jegg AM, Bröske AM, Dembowski M, Bray-French K, Freilinger C, Meneses-Lorente G, Baehner M, Harding R, Ratnayake J, Abiraj K, Gass N, Noh K, Christen RD, Ukarma L, Bompas E, Delord JP, Blay JY, Rüttinger D. CSF1R inhibition with emactuzumab in locally advanced diffuse-type tenosynovial giant cell tumours of the soft tissue: a dose-escalation and dose-expansion phase 1 study. Lancet Oncol 2015; 16:949-56.
    • Enasidenib
    • IDH2
    • 1B Stein EM, DiNardo CD, Pollyea DA, Fathi AT, Roboz GJ, Altman JK, Stone RM, DeAngelo DJ, Levine RL, Flinn IW, Kantarjian HM, Collins R, Patel MR, Frankel AE, Stein A, Sekeres MA, Swords RT, Medeiros BC, Willekens C, Vyas P, Tosolini A, Xu Q, Knight RD, Yen KE, Agresta S, de Botton S, Tallman MS. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood 2017; 130:722-731.
    • IDH2
    • 3 Stein EM, Fathi AT, DiNardo CD, Pollyea DA, Roboz GJ, Collins R, Sekeres MA, Stone RM, Attar EC, Frattini MG, Tosolini A, Xu Q, See WL, MacBeth KJ, de Botton S, Tallman MS, Kantarjian HM. Enasidenib in patients with mutant IDH2 myelodysplastic syndromes: a phase 1 subgroup analysis of the multicentre, AG221-C-001 trial. Lancet Haematol 2020; 7:e309-e319.
    • IDH2
    • 4 Yen K, Travins J, Wang F, David MD, Artin E, Straley K, Padyana A, Gross S, DeLaBarre B, Tobin E, Chen Y, Nagaraja R, Choe S, Jin L, Konteatis Z, Cianchetta G, Saunders JO, Salituro FG, Quivoron C, Opolon P, Bawa O, Saada V, Paci A, Broutin S, Bernard OA, de Botton S, Marteyn BS, Pilichowska M, Xu Y, Fang C, Jiang F, Wei W, Jin S, Silverman L, Liu W, Yang H, Dang L, Dorsch M, Penard-Lacronique V, Biller SA, Su SM. AG-221, a First-in-Class Therapy Targeting Acute Myeloid Leukemia Harboring Oncogenic IDH2 Mutations. Cancer Discov 2017; 7:478-493.
    • Enasidenib + Azacitidine
    • IDH2
    • 3 DiNardo CD, Schuh AC, Stein EM, Montesinos P, Wei AH, de Botton S, Zeidan AM, Fathi AT, Kantarjian HM, Bennett JM, Frattini MG, Martin-Regueira P, Lersch F, Gong J, Hasan M, Vyas P, Döhner H. Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial. Lancet Oncol 2021 Oct 18. pii: S1470-2045(21)00494-0. [Epub ahead of print]
    • Encorafenib + Binimetinib
    • BRAF
    • 3 Sullivan RJ, Weber J, Patel S, Dummer R, Carlino MS, Tan DSW, Lebbé C, Siena S, Elez E, Wollenberg L, Pickard MD, Sandor V, Ascierto PA. A Phase Ib/II Study of the BRAF Inhibitor Encorafenib Plus the MEK Inhibitor Binimetinib in Patients with BRAFV600E/K -mutant Solid Tumors. Clin Cancer Res 2020; 26:5102-5112.
    • Encorafenib + Binimetinib + Cetuximab
    • BRAF+MET
    • R2 Akhoundova D, Pietge H, Hussung S, Kiessling M, Britschgi C, Zoche M, Rechsteiner M, Weber A, Fritsch RM. Targeting Secondary and Tertiary Resistance to BRAF Inhibition in BRAF V600E-mutated Metastatic Colorectal Cancer. JCO Prec Oncol 2021; 10.1200/PO.21.00107 5 1082-1087. Published online July 1, 2021.
    • Encorafenib + Capmatinib
    • BRAF+MET
    • 4 Akhoundova D, Pietge H, Hussung S, Kiessling M, Britschgi C, Zoche M, Rechsteiner M, Weber A, Fritsch RM. Targeting Secondary and Tertiary Resistance to BRAF Inhibition in BRAF V600E-mutated Metastatic Colorectal Cancer. JCO Prec Oncol 2021; 10.1200/PO.21.00107 5 1082-1087. Published online July 1, 2021.
    • Encorafenib + Cetuximab
    • BRAF+MET
    • R2 Akhoundova D, Pietge H, Hussung S, Kiessling M, Britschgi C, Zoche M, Rechsteiner M, Weber A, Fritsch RM. Targeting Secondary and Tertiary Resistance to BRAF Inhibition in BRAF V600E-mutated Metastatic Colorectal Cancer. JCO Prec Oncol 2021; 10.1200/PO.21.00107 5 1082-1087. Published online July 1, 2021.
    • BRAF
    • 1 Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, Wasan H, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Pfeiffer P, Orlov S, Lonardi S, Elez E, Kim TW, Schellens JHM, Guo C, Krishnan A, Dekervel J, Morris V, Calvo Ferrandiz A, Tarpgaard LS, Braun M, Gollerkeri A, Keir C, Maharry K, Pickard M, Christy-Bittel J, Anderson L, Sandor V, Tabernero J. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. N Engl J Med 2019; 381:1632-1643.
    • 1 Tabernero J, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, Desai J, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Elez E, Gollerkeri A, Maharry K, Christy-Bittel J, Kopetz S. Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study. J Clin Oncol 2021; 39:273-284.
    • Enfortumab Vedotin
    • NECTIN4
    • 2 Rosenberg JE, O'Donnell PH, Balar AV, McGregor BA, Heath EI, Yu EY, Galsky MD, Hahn NM, Gartner EM, Pinelli JM, Liang SY, Melhem-Bertrandt A, Petrylak DP. Pivotal Trial of Enfortumab Vedotin in Urothelial Carcinoma After Platinum and Anti-Programmed Death 1/Programmed Death Ligand 1 Therapy. J Clin Oncol 2019; 37:2592-2600.
    • 2 Powles T, Rosenberg JE, Sonpavde GP, Loriot Y, Durán I, Lee JL, Matsubara N, Vulsteke C, Castellano D, Wu C, Campbell M, Matsangou M, Petrylak DP. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med 2021 Feb 12. [Epub ahead of print]
    • NECTIN4
    • 4 Rosenberg J, Sridhar SS, Zhang J, Smith D, Ruether D, Flaig TW, Baranda J, Lang J, Plimack ER, Sangha R, Heath EI, Merchan J, Quinn DI, Srinivas S, Milowsky M, Wu C, Gartner EM, Zuo P, Melhem-Bertrandt A, Petrylak DP. EV-101: A Phase I Study of Single-Agent Enfortumab Vedotin in Patients With Nectin-4-Positive Solid Tumors, Including Metastatic Urothelial Carcinoma. J Clin Oncol 2020; 38:1041-1049.
    • Enfortumab vedotin
    • NECTIN4
    • 4 Chu C, Sjöström M, Egusa EA, Gibb E, Badura ML, Koshkin VS, Stohr BA, Meng M, Pruthi R, Friedlander TW, Lotan Y, Black PC, Porten SP, Feng FY, Chou J. Heterogeneity in Nectin-4 expression across molecular subtypes of urothelial cancer mediates sensitivity to enfortumab vedotin. J Clin Oncol 2021; 39(6_suppl): 463-463.
    • Enobosarm
    • AR+ESR1
    • 3 Palmieri C, Linden HM, Birrell S, Lim E, Schwartzberg LS, Rugo HS, Cobb PW, Jain K, Vogel CL, O'Shaughnessy J, Johnston SRD, Getzenberg RH, Barnette KG, Steiner MS, Brufsky A, Overmoyer B. Efficacy of enobosarm, a selective androgen receptor (AR) targeting agent, correlates with the degree of AR positivity in advanced AR+/estrogen receptor (ER)+ breast cancer in an international phase 2 clinical study. J Clin Oncol 2021; 39(15_suppl): 1020-1020.
    • Ensartinib
    • ROS1
    • R2 Davare MA, Vellore NA, Wagner JP, Eide CA, Goodman JR, Drilon A, Deininger MW, O'Hare T, Druker BJ. Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors. Proc Natl Acad Sci U S A 2015; 112:E5381-90.
    • R2 Guisier F, Piton N, Salaun M, Thiberville L. ROS1-rearranged NSCLC With Secondary Resistance Mutation: Case Report and Current Perspectives. Clin Lung Cancer 2019; 20:e593-e596.
    • ALK
    • R2 Delmonte A, Burgio MA, Verlicchi A, Bronte G, Cravero P, Ulivi P, Martinelli G, Crinò L. New generation anaplastic lymphoma kinase inhibitors. Transl Lung Cancer Res 2019; 8(Suppl 3):S280-S289.
    • ALK
    • 2 Horn L, Wang Z, Wu G, Poddubskaya E, Mok T, Reck M, Wakelee H, Chiappori AA, Lee DH, Breder V, Orlov S, Cicin I, Cheng Y, Liu Y, Fan Y, Whisenant JG, Zhou Y, Oertel V, Harrow K, Liang C, Mao L, Selvaggi G, Wu YL. Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Randomized Clinical Trial. JAMA Oncol 2021; 7:1617-1625.
    • ALK
    • 3 Lin JJ, Riely GJ, Shaw AT. Targeting ALK: Precision Medicine Takes on Drug Resistance. Cancer Discov 2017; 7:137-155.
    • 3 Yang Y, Zhou J, Zhou J, Feng J, Zhuang W, Chen J, Zhao J, Zhong W, Zhao Y, Zhang Y, Song Y, Hu Y, Yu Z, Gong Y, Chen Y, Ye F, Zhang S, Cao L, Fan Y, Wu G, Guo Y, Zhou C, Ma K, Fang J, Feng W, Liu Y, Zheng Z, Li G, Wu N, Song W, Liu X, Zhao S, Ding L, Mao L, Selvaggi G, Yuan X, Fu Y, Wang T, Xiao S, Zhang L. Efficacy, safety, and biomarker analysis of ensartinib in crizotinib-resistant, ALK-positive non-small-cell lung cancer: a multicentre, phase 2 trial. Lancet Respir Med 2020; 8:45-53.
    • ROS1
    • 4 X-396 Capsule in Advanced NSCLC Patients With ROS1 Gene Rearrangement [NCT03608007]
    • ALK
    • 4 Gainor JF, Tan DS, De Pas T, Solomon BJ, Ahmad A, Lazzari C, de Marinis F, Spitaleri G, Schultz K, Friboulet L, Yeap BY, Engelman JA, Shaw AT. Progression-Free and Overall Survival in ALK-Positive NSCLC Patients Treated with Sequential Crizotinib and Ceritinib. Clin Cancer Res 2015; 21:2745-52.
    • 4 Yang Y, Zhou J, Zhou J, Feng J, Zhuang W, Chen J, Zhao J, Zhong W, Zhao Y, Zhang Y, Song Y, Hu Y, Yu Z, Gong Y, Chen Y, Ye F, Zhang S, Cao L, Fan Y, Wu G, Guo Y, Zhou C, Ma K, Fang J, Feng W, Liu Y, Zheng Z, Li G, Wu N, Song W, Liu X, Zhao S, Ding L, Mao L, Selvaggi G, Yuan X, Fu Y, Wang T, Xiao S, Zhang L. Efficacy, safety, and biomarker analysis of ensartinib in crizotinib-resistant, ALK-positive non-small-cell lung cancer: a multicentre, phase 2 trial. Lancet Respir Med 2020; 8:45-53.
    • 4 Delmonte A, Burgio MA, Verlicchi A, Bronte G, Cravero P, Ulivi P, Martinelli G, Crinò L. New generation anaplastic lymphoma kinase inhibitors. Transl Lung Cancer Res 2019; 8(Suppl 3):S280-S289.
    • Entinostat + Exemestane
    • ESR1
    • R2 Yardley DA, Ismail-Khan RR, Melichar B, Lichinitser M, Munster PN, Klein PM, Cruickshank S, Miller KD, Lee MJ, Trepel JB. Randomized phase II, double-blind, placebo-controlled study of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on treatment with a nonsteroidal aromatase inhibitor. J Clin Oncol 2013; 31:2128-35.
    • R2 A Trial of the ECOG-ACRIN Cancer Research Group. E2112: Randomized Phase III Trial of Endocrine Therapy Plus Entinostat or Placebo in Hormone Receptor-Positive Advanced Breast Cancer.. J Clin Oncol 2021; 39:3171-3181.
    • Entrectinib
    • ROS1
    • 1 Braud FGD, Niger M, Damian S, Bardazza B, Martinetti A, Pelosi G, Marrapese G, Palmeri L, Cerea G, Valtorta E, Veronese S, Sartore-Bianchi A, Ardini E, Isachi A, Martignoni M, Galvani A, Luo D, Yeh L, Senderowicz AM, Siena S. Alka-372-001: First-in-human, phase I study of entrectinib - an oral pan-trk, ROS1, and ALK inhibitor in patients with advanced solid tumors with relevant molecular alterations. J Clin Oncol 2015; 33(15_suppl): 2517-2517.
    • 1 Drilon A, Siena S, Ou SI, Patel M, Ahn MJ, Lee J, Bauer TM, Farago AF, Wheler JJ, Liu SV, Doebele R, Giannetta L, Cerea G, Marrapese G, Schirru M, Amatu A, Bencardino K, Palmeri L, Sartore-Bianchi A, Vanzulli A, Cresta S, Damian S, Duca M, Ardini E, Li G, Christiansen J, Kowalski K, Johnson AD, Patel R, Luo D, Chow-Maneval E, Hornby Z, Multani PS, Shaw AT, De Braud FG. Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1). Cancer Discov 2017; 7:400-409.
    • 1 Drilon A, Siena S, Dziadziuszko R, Barlesi F, Krebs MG, Shaw AT, de Braud F, Rolfo C, Ahn MJ, Wolf J, Seto T, Cho BC, Patel MR, Chiu CH, John T, Goto K, Karapetis CS, Arkenau HT, Kim SW, Ohe Y, Li YC, Chae YK, Chung CH, Otterson GA, Murakami H, Lin CC, Tan DSW, Prenen H, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Doebele RC; trial investigators. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials. Lancet Oncol 2020; 21:261-270.
    • NTRK1, NTRK2, NTRK3
    • 1B Doebele RC, Drilon A, Paz-Ares L, Siena S, Shaw AT, Farago AF, Blakely CM, Seto T, Cho BC, Tosi D, Besse B, Chawla SP, Bazhenova L, Krauss JC, Chae YK, Barve M, Garrido-Laguna I, Liu SV, Conkling P, John T, Fakih M, Sigal D, Loong HH, Buchschacher GL Jr, Garrido P, Nieva J, Steuer C, Overbeck TR, Bowles DW, Fox E, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Demetri GD; trial investigators. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. Lancet Oncol 2020; 21:271-282.
    • NTRK1, NTRK3
    • R1 Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 2018; 15:731-747.
    • ROS1
    • R2 Davare MA, Vellore NA, Wagner JP, Eide CA, Goodman JR, Drilon A, Deininger MW, O'Hare T, Druker BJ. Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors. Proc Natl Acad Sci U S A 2015; 112:E5381-90.
    • ALK
    • R2 Lin JJ, Riely GJ, Shaw AT. Targeting ALK: Precision Medicine Takes on Drug Resistance. Cancer Discov 2017; 7:137-155.
    • KRAS
    • R2 Ku BM, Bae YH, Lee KY, Sun JM, Lee SH, Ahn JS, Park K, Ahn MJ. Entrectinib resistance mechanisms in ROS1-rearranged non-small cell lung cancer. Invest New Drugs 2020; 38:360-368.
    • ROS1
    • R2 Guisier F, Piton N, Salaun M, Thiberville L. ROS1-rearranged NSCLC With Secondary Resistance Mutation: Case Report and Current Perspectives. Clin Lung Cancer 2019; 20:e593-e596.
    • NTRK1, NTRK2, NTRK3
    • 3 . . [DOI:]
    • ALK
    • 3 Braud FGD, Niger M, Damian S, Bardazza B, Martinetti A, Pelosi G, Marrapese G, Palmeri L, Cerea G, Valtorta E, Veronese S, Sartore-Bianchi A, Ardini E, Isachi A, Martignoni M, Galvani A, Luo D, Yeh L, Senderowicz AM, Siena S. Alka-372-001: First-in-human, phase I study of entrectinib - an oral pan-trk, ROS1, and ALK inhibitor in patients with advanced solid tumors with relevant molecular alterations. J Clin Oncol 2015; 33(15_suppl): 2517-2517.
    • 3 Lin JJ, Riely GJ, Shaw AT. Targeting ALK: Precision Medicine Takes on Drug Resistance. Cancer Discov 2017; 7:137-155.
    • NTRK1, ROS1
    • 4 Pishvaian MJ, Garrido-Laguna I, Liu SV, Multani PS, Chow-Maneval E, Rolfo C. Entrectinib in TRK and ROS1 Fusion-Positive Metastatic Pancreatic Cancer. JCO Prec Oncol 2018; 10.1200/PO.18.00039 - published online July 25, 2018
    • ROS1
    • 4 Study of Oral RXDX-101 in Adult Patients With Locally Advanced or Metastatic Cancer Targeting NTRK1, NTRK2, NTRK3, ROS1, or ALK Molecular Alterations. [NCT02097810]
    • 4 Brigatinib in Treating Patients With ALK and ROS1 Gene Alterations and Locally Advanced or Metastatic Solid Cancers [NCT03868423]
    • 4 A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations [NCT04094610]
    • ALK
    • 4 Awad MM, Shaw AT. ALK inhibitors in non-small cell lung cancer: crizotinib and beyond. Clin Adv Hematol Oncol 2014; 12:429-39
    • 4 Davare MA, Vellore NA, Wagner JP, Eide CA, Goodman JR, Drilon A, Deininger MW, O'Hare T, Druker BJ. Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors. Proc Natl Acad Sci U S A 2015; 112:E5381-90.
    • 4 Menichincheri M, Ardini E, Magnaghi P, Avanzi N, Banfi P, Bossi R, Buffa L, Canevari G, Ceriani L, Colombo M, Corti L, Donati D, Fasolini M, Felder E, Fiorelli C, Fiorentini F, Galvani A, Isacchi A, Borgia AL, Marchionni C, Nesi M, Orrenius C, Panzeri A, Pesenti E, Rusconi L, Saccardo MB, Vanotti E, Perrone E, Orsini P. Discovery of Entrectinib: A New 3-Aminoindazole As a Potent Anaplastic Lymphoma Kinase (ALK), c-ros Oncogene 1 Kinase (ROS1), and Pan-Tropomyosin Receptor Kinases (Pan-TRKs) inhibitor. J Med Chem 2016; 59:3392-408.
    • 4 Ono A, Murakami H, Serizawa M, Wakuda K, Kenmotsu H, Naito T, Taira T, Koh Y, Ohde Y, Nakajima T, Endo M, Takahashi T. Drastic initial response and subsequent response to two ALK inhibitors in a patient with a highly aggressive ALK-rearranged inflammatory myofibroblastic tumor arising in the pleural cavity. Lung Cancer 2016; 99:151-4.
    • ROS1
    • 4 Drilon A, Siena S, Ou SI, Patel M, Ahn MJ, Lee J, Bauer TM, Farago AF, Wheler JJ, Liu SV, Doebele R, Giannetta L, Cerea G, Marrapese G, Schirru M, Amatu A, Bencardino K, Palmeri L, Sartore-Bianchi A, Vanzulli A, Cresta S, Damian S, Duca M, Ardini E, Li G, Christiansen J, Kowalski K, Johnson AD, Patel R, Luo D, Chow-Maneval E, Hornby Z, Multani PS, Shaw AT, De Braud FG. Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1). Cancer Discov 2017; 7:400-409.
    • 4 Liu SV, Macke LA, Colton BS, Imran SS, Christiansen J, Chow-Maneval E, Hornby Z, Multani PS. Response to Entrectinib in Differentiated Thyroid Cancer With a ROS1 Fusion. JCO Precis Oncol 2017; 1. pii: PO.17.00105. eCollection 2017.
    • NTRK3
    • 4 Ogura K, Somwar R, Hmeljak J, Magnan H, Benayed R, Momeni Boroujeni A, Bowman AS, Mattar MS, Khodos I, de Stanchina E, Jungbluth A, Asher M, Odintsov I, Hartono AB, LaQuaglia MP, Slotkin E, Pratilas CA, Lee SB, Spraggon L, Ladanyi M. Therapeutic Potential of NTRK3 Inhibition in Desmoplastic Small Round Cell Tumor. Clin Cancer Res 2021; 27:1184-1194.
    • Enzalutamide
    • AR
    • R2 Ho AL, Foster NR, Zoroufy AJ, Worden FP, Price KAR, Adkins D, Bowles DW, Kang H, Burtness B, Sherman EJ, Morton RF, Katabi N, Munster PN, Schwartz GK. Alliance A091404: A phase II study of enzalutamide (NSC# 766085) for patients with androgen receptor-positive salivary cancers. J Clin Oncol 2019; 37(15_suppl): 6020-6020.
    • R2 Korpal M, Korn JM, Gao X, Rakiec DP, Ruddy DA, Doshi S, Yuan J, Kovats SG, Kim S, Cooke VG, Monahan JE, Stegmeier F, Roberts TM, Sellers WR, Zhou W, Zhu P. An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide). Cancer Discov 2013; 3:1030-43.
    • R2 Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, Chen Y, Mohammad TA, Chen Y, Fedor HL, Lotan TL, Zheng Q, De Marzo AM, Isaacs JT, Isaacs WB, Nadal R, Paller CJ, Denmeade SR, Carducci MA, Eisenberger MA, Luo J. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 2014; 371:1028-38.
    • AR, AURKA, MYCN, RB1, TP53
    • R2 Watson PA, Arora VK, Sawyers CL. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nat Rev Cancer 2015; 15:701-11.
    • AR
    • R2 Lallous N, Volik SV, Awrey S, Leblanc E, Tse R, Murillo J, Singh K, Azad AA, Wyatt AW, LeBihan S, Chi KN, Gleave ME, Rennie PS, Collins CC, Cherkasov A. Functional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients. Genome Biol 2016; 17:10.
    • AR
    • 3 Traina TA, Miller K, Yardley DA, O'Shaughnessy J, Cortes J, Awada A, Kelly CM, Trudeau ME, Schmid P, Gianni L, Garcia-Estevez L, Nanda R, Ademuyiwa FO, Chan S, Steinberg JL, Blaney ME, Tudor IC, Uppal H, Peterson AC, Hudis CA. Results from a phase 2 study of enzalutamide (ENZA), an androgen receptor (AR) inhibitor, in advanced AR+ triple-negative breast cancer (TNBC). J Clin Oncol 2015; 33(15_suppl): 1003-1003.
    • Eprenetapopt + Azacitidine
    • TP53
    • 3 Sallman DA, DeZern AE, Garcia-Manero G, Steensma DP, Roboz GJ, Sekeres MA, Cluzeau T, Sweet KL, McLemore A, McGraw KL, Puskas J, Zhang L, Yao J, Mo Q, Nardelli L, Al Ali NH, Padron E, Korbel G, Attar EC, Kantarjian HM, Lancet JE, Fenaux P, List AF, Komrokji RS. Eprenetapopt (APR-246) and Azacitidine in TP53-Mutant Myelodysplastic Syndromes. J Clin Oncol 2021 Jan 15:JCO2002341. [Epub ahead of print]
    • Erdafitinib
    • FGFR2, FGFR3
    • 2 Loriot Y, Necchi A, Park SH, Garcia-Donas J, Huddart R, Burgess E, Fleming M, Rezazadeh A, Mellado B, Varlamov S, Joshi M, Duran I, Tagawa ST, Zakharia Y, Zhong B, Stuyckens K, Santiago-Walker A, De Porre P, O'Hagan A, Avadhani A, Siefker-Radtke AO; BLC2001 Study Group. Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma. N Engl J Med 2019; 381:338-348.
    • FGFR2
    • 3 Park JO, Feng Y, Chen Y, Su W, Oh D, Shen L, Kim K, Liu X, Bai Y, Liao H, Nie J, Qing M, Ji Q, Li J, Zhao M, Porre PD, Monga M, PA EDJCR&DCSCJR&DBBCOJRUS. Updated results of a phase IIa study to evaluate the clinical efficacy and safety of erdafitinib in Asian advanced cholangiocarcinoma (CCA) patients with FGFR alterations. J Clin Oncol 2019; 37(15_suppl): 4117-4117.
    • FGFR1, FGFR2, FGFR3
    • 3 Loriot Y, Schuler MH, Iyer G, Witt O, Doi T, Qin S, Tabernero J, Reardon DA, Massard C, Palmer D, Lugowska I, Coward J, Corassa M, Stuyckens K, Liao H, Najmi S, Hammond C, Santiago-Walker AE, Sweiti H, Pant S, Center APACC, Paulo S, Development BJR&, House S, Therapeutics PDoIC, Center TUoTMAC, Houston , TX . Tumor agnostic efficacy and safety of erdafitinib in patients (pts) with advanced solid tumors with prespecified fibroblast growth factor receptor alterations (FGFRalt) in RAGNAR: Interim analysis (IA) results. J Clin Oncol 2022; 40(16_suppl): 3007-3007.
    • FGFR1, FGFR2, FGFR3
    • 4 Nogova L, Malchers F, Zadoyan G, Hillmer A, Merkelbach-Bruse S, Riedel R, Michels S, Masouleh BK, Porre PD, Santiago-Walker A, Scheffler M, Fischer R, Abdulla D, Thomas R, Büttner R, Wolf J. P1.01-72 FIND Trial: A Phase II Study to Evaluate the Efficacy of the FGFR-Inhibitor Erdafitinib in FGFR-Mutated and -Translocated Squamous NSCLC. J Thorac Oncol 2018; 13 (10): S490. 10.1016/j.jtho.2018.08.628
    • FGFR2
    • 4 Argueta SAU, Hanna NH. Remarkable Response to Erdafitinib in Metastatic Lung Adenocarcinoma With FGFR Fusion. JCO Prec Oncol 2020; 10.1200/PO.20.00110 4 823-824. Published online July 16, 2020.
    • FGFR1, FGFR2, FGFR3
    • 4 A Study of Erdafitinib in Participants With Advanced Solid Tumors and Fibroblast Growth Factor Receptor (FGFR) Gene Alterations [NCT04083976]
    • 4 Bahleda R, Italiano A, Hierro C, Mita A, Cervantes A, Chan N, Awad M, Calvo E, Moreno V, Govindan R, Spira A, Gonzalez M, Zhong B, Santiago-Walker A, Poggesi I, Parekh T, Xie H, Infante J, Tabernero J. Multicenter Phase I Study of Erdafitinib (JNJ-42756493), Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients with Advanced or Refractory Solid Tumors. Clin Cancer Res 2019; 25:4888-4897.
    • FGFR2
    • 4 Urrutia Argueta SA, Hanna NH. Remarkable Response to Erdafitinib in Metastatic Lung Adenocarcinoma With FGFR Fusion. JCO Precis Oncol 2020; 4:823-824.
    • Erdafitinib, Pemigatinib
    • FGFR2
    • 4 Sootome H, Fujita H, Ito K, Ochiiwa H, Fujioka Y, Ito K, Miura A, Sagara T, Ito S, Ohsawa H, Otsuki S, Funabashi K, Yashiro M, Matsuo K, Yonekura K, Hirai H. Futibatinib Is a Novel Irreversible FGFR 1-4 Inhibitor That Shows Selective Antitumor Activity against FGFR-Deregulated Tumors. Cancer Res 2020; 80:4986-4997.
    • Erlotinib
    • EGFR
    • R1 Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong KK, Meyerson M, Eck MJ. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A 2008; 105:2070-5.
    • R1 Yasuda H, Kobayashi S, Costa DB. EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications. Lancet Oncol 2012; 13:e23-31.
    • EGFR
    • R2 Wu JY, Yu CJ, Chang YC, Yang CH, Shih JY, Yang PC. Effectiveness of tyrosine kinase inhibitors on "uncommon" epidermal growth factor receptor mutations of unknown clinical significance in non-small cell lung cancer. Clin Cancer Res 2011; 17:3812-21.
    • BCL2L11
    • R2 Ng KP, Hillmer AM, Chuah CT, Juan WC, Ko TK, Teo AS, Ariyaratne PN, Takahashi N, Sawada K, Fei Y, Soh S, Lee WH, Huang JW, Allen JC Jr, Woo XY, Nagarajan N, Kumar V, Thalamuthu A, Poh WT, Ang AL, Mya HT, How GF, Yang LY, Koh LP, Chowbay B, Chang CT, Nadarajan VS, Chng WJ, Than H, Lim LC, Goh YT, Zhang S, Poh D, Tan P, Seet JE, Ang MK, Chau NM, Ng QS, Tan DS, Soda M, Isobe K, Nöthen MM, Wong TY, Shahab A, Ruan X, Cacheux-Rataboul V, Sung WK, Tan EH, Yatabe Y, Mano H, Soo RA, Chin TM, Lim WT, Ruan Y, Ong ST. A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer. Nat Med 2012; 18:521-8.
    • ERBB2
    • R2 Yu HA, Arcila ME, Rekhtman N, Sima CS, Zakowski MF, Pao W, Kris MG, Miller VA, Ladanyi M, Riely GJ. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res 2013; 19:2240-7.
    • EGFR
    • R2 Yasuda H, Park E, Yun CH, Sng NJ, Lucena-Araujo AR, Yeo WL, Huberman MS, Cohen DW, Nakayama S, Ishioka K, Yamaguchi N, Hanna M, Oxnard GR, Lathan CS, Moran T, Sequist LV, Chaft JE, Riely GJ, Arcila ME, Soo RA, Meyerson M, Eck MJ, Kobayashi SS, Costa DB. Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer. Sci Transl Med 2013; 5:216ra177.
    • R2 Matsushima S, Ohtsuka K, Ohnishi H, Fujiwara M, Nakamura H, Morii T, Kishino T, Goto H, Watanabe T. V843I, a lung cancer predisposing EGFR mutation, is responsible for resistance to EGFR tyrosine kinase inhibitors. J Thorac Oncol 2014; 9:1377-84.
    • EGFR+RB1
    • R2 Niederst MJ, Sequist LV, Poirier JT, Mermel CH, Lockerman EL, Garcia AR, Katayama R, Costa C, Ross KN, Moran T, Howe E, Fulton LE, Mulvey HE, Bernardo LA, Mohamoud F, Miyoshi N, VanderLaan PA, Costa DB, Jänne PA, Borger DR, Ramaswamy S, Shioda T, Iafrate AJ, Getz G, Rudin CM, Mino-Kenudson M, Engelman JA. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat Commun 2015; 6:6377.
    • EGFR+ROS1
    • R2 Zeng L, Yang N, Zhang Y. GOPC-ROS1 Rearrangement as an Acquired Resistance Mechanism to Osimertinib and Responding to Crizotinib Combined Treatments in Lung Adenocarcinoma. J Thorac Oncol 2018; 13:e114-e116.
    • EGFR+RET
    • R2 Piotrowska Z, Isozaki H, Lennerz JK, Gainor JF, Lennes IT, Zhu VW, Marcoux N, Banwait MK, Digumarthy SR, Su W, Yoda S, Riley AK, Nangia V, Lin JJ, Nagy RJ, Lanman RB, Dias-Santagata D, Mino-Kenudson M, Iafrate AJ, Heist RS, Shaw AT, Evans EK, Clifford C, Ou SI, Wolf B, Hata AN, Sequist LV. Landscape of Acquired Resistance to Osimertinib in EGFR-Mutant NSCLC and Clinical Validation of Combined EGFR and RET Inhibition with Osimertinib and BLU-667 for Acquired RET Fusion. Cancer Discov 2018; 8:1529-1539.
    • EGFR+RB1, EGFR+TP53
    • R2 Marcoux N, Gettinger SN, O'Kane G, Arbour KC, Neal JW, Husain H, Evans TL, Brahmer JR, Muzikansky A, Bonomi PD, Del Prete S, Wurtz A, Farago AF, Dias-Santagata D, Mino-Kenudson M, Reckamp KL, Yu HA, Wakelee HA, Shepherd FA, Piotrowska Z, Sequist LV. EGFR-Mutant Adenocarcinomas That Transform to Small-Cell Lung Cancer and Other Neuroendocrine Carcinomas: Clinical Outcomes. J Clin Oncol 2019; 37:278-285.
    • MET
    • R2 Lai GGY, Lim TH, Lim J, Liew PJR, Kwang XL, Nahar R, Aung ZW, Takano A, Lee YY, Lau DPX, Tan GS, Tan SH, Tan WL, Ang MK, Toh CK, Tan BS, Devanand A, Too CW, Gogna A, Ong BH, Koh TPT, Kanesvaran R, Ng QS, Jain A, Rajasekaran T, Yuan J, Lim TKH, Lim AST, Hillmer AM, Lim WT, Iyer NG, Tam WL, Zhai W, Tan EH, Tan DSW. Clonal MET Amplification as a Determinant of Tyrosine Kinase Inhibitor Resistance in Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer. J Clin Oncol 2019; 37:876-884.
    • EGFR+ALK, EGFR+RET
    • R2 Offin M, Somwar R, Rekhtman N, Benayed R, Chang JC, Plodkowski A, Lui AJW, Eng J, Rosenblum M, Li BT, Riely GJ, Rudin CM, Kris MG, Travis W, Drilon A, Arcila ME, Ladanyi M, Yu HA. Acquired ALK and RET Gene Fusions as Mechanisms of Resistance to Osimertinib in EGFR-Mutant Lung Cancers. JCO Precis Oncol 2018;2.
    • EGFR
    • R2 Truini A, Starrett JH, Stewart T, Ashtekar K, Walther Z, Wurtz A, Lu D, Park JH, DeVeaux M, Song X, Gettinger S, Zelterman D, Lemmon MA, Goldberg SB, Politi K. The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma. Clin Cancer Res 2019; 25:6382-6391.
    • R2 Liang SK, Ko JC, Yang JC, Shih JY. Afatinib is effective in the treatment of lung adenocarcinoma with uncommon EGFR p.L747P and p.L747S mutations. Lung Cancer 2019; 133:103-109.
    • R2 Li Y, Zhang HB, Chen X, Yang X, Ye Y, Bekaii-Saab T, Zheng Y, Zhang Y. A Rare EGFR-SEPT14 Fusion in a Patient with Colorectal Adenocarcinoma Responding to Erlotinib. Oncologist 2020; 25:203-207.
    • R2 Xu H, Li W, Yang G, Li J, Yang L, Xu F, Yang Y, Ying J, Wang Y. Heterogeneous Response to First-Generation Tyrosine Kinase Inhibitors in Non-Small-Cell Lung Cancers with Different EGFR Exon 19 Mutations. Target Oncol 2020; 15:357-364.
    • R2 Lee C, Kim M, Kim DW, Kim TM, Kim S, Im SW, Jeon YK, Keam B, Ku JL, Heo DS. Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non-Small Cell Lung Cancer. Cancer Res Treat 2021 May 3. [Epub ahead of print]
    • R2 Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 2021; 597:732-737.
    • EGFR
    • 1 Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005; 353:123-32.
    • 1 Tsao MS, Sakurada A, Cutz JC, Zhu CQ, Kamel-Reid S, Squire J, Lorimer I, Zhang T, Liu N, Daneshmand M, Marrano P, da Cunha Santos G, Lagarde A, Richardson F, Seymour L, Whitehead M, Ding K, Pater J, Shepherd FA. Erlotinib in lung cancer - molecular and clinical predictors of outcome. N Engl J Med 2005; 353:133-44.
    • EGFR
    • 2 Gergis C, Rangachari D, Fujii M, Varkaris A, VanderLaan PA, Kobayashi S, Costa DB. EGFR-A763_Y764insFQEA: A unique exon 20 insertion mutation that displays sensitivity to all classes of approved lung cancer EGFR tyrosine kinase inhibitors. J Clin Oncol 2019; 37(15_suppl):
    • 2 Costa DB. Kinase inhibitor-responsive genotypes in EGFR mutated lung adenocarcinomas: moving past common point mutations or indels into uncommon kinase domain duplications and rearrangements. Transl Lung Cancer Res 2016; 5:331-7.
    • 2 Li K, Yang M, Liang N, Li S. Determining EGFR-TKI sensitivity of G719X and other uncommon EGFR mutations in non-small cell lung cancer: Perplexity and solution (Review). Oncol Rep 2017; 37:1347-1358.
    • EGFR
    • 3 Lin YT, Liu YN, Wu SG, Yang JC, Shih JY. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor-sensitive Exon 19 Insertion and Exon 20 Insertion in Patients With Advanced Non-Small-cell Lung Cancer. Clin Lung Cancer 2017; 18:324-332.e1.
    • 3 Zhu C, Zhuang W, Chen L, Yang W, Ou WB. Frontiers of ctDNA, targeted therapies, and immunotherapy in non-small-cell lung cancer. Transl Lung Cancer Res 2020; 9:111-138.
    • EGFR
    • 4 Ozer BH, Wiepz GJ, Bertics PJ. Activity and cellular localization of an oncogenic glioblastoma multiforme-associated EGF receptor mutant possessing a duplicated kinase domain. Oncogene 2010; 29:855-64.
    • 4 Wang F, Fu S, Shao Q, Zhou YB, Zhang X, Zhang X, Xue C, Lin JG, Huang LX, Zhang L, Zhang WM, Shao JY. High EGFR copy number predicts benefits from tyrosine kinase inhibitor treatment for non-small cell lung cancer patients with wild-type EGFR. J Transl Med 2013; 11:90.
    • ERRFI1
    • 4 Borad MJ, Champion MD, Egan JB, Liang WS, Fonseca R, Bryce AH, McCullough AE, Barrett MT, Hunt K, Patel MD, Young SW, Collins JM, Silva AC, Condjella RM, Block M, McWilliams RR, Lazaridis KN, Klee EW, Bible KC, Harris P, Oliver GR, Bhavsar JD, Nair AA, Middha S, Asmann Y, Kocher JP, Schahl K, Kipp BR, Barr Fritcher EG, Baker A, Aldrich J, Kurdoglu A, Izatt T, Christoforides A, Cherni I, Nasser S, Reiman R, Phillips L, McDonald J, Adkins J, Mastrian SD, Placek P, Watanabe AT, Lobello J, Han H, Von Hoff D, Craig DW, Stewart AK, Carpten JD. Integrated genomic characterization reveals novel, therapeutically relevant drug targets in FGFR and EGFR pathways in sporadic intrahepatic cholangiocarcinoma. PLoS Genet 2014; 10:e1004135. eCollection 2014 Feb.
    • EGFR
    • 4 Kobayashi Y, Togashi Y, Yatabe Y, Mizuuchi H, Jangchul P, Kondo C, Shimoji M, Sato K, Suda K, Tomizawa K, Takemoto T, Hida T, Nishio K, Mitsudomi T. EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIs. Clin Cancer Res 2015; 21:5305-13.
    • 4 Gallant JN, Sheehan JH, Shaver TM, Bailey M, Lipson D, Chandramohan R, Red Brewer M, York SJ, Kris MG, Pietenpol JA, Ladanyi M, Miller VA, Ali SM, Meiler J, Lovly CM. EGFR Kinase Domain Duplication (EGFR-KDD) Is a Novel Oncogenic Driver in Lung Cancer That Is Clinically Responsive to Afatinib. Cancer Discov 2015; 5:1155-63.
    • 4 Konduri K, Gallant JN, Chae YK, Giles FJ, Gitlitz BJ, Gowen K, Ichihara E, Owonikoko TK, Peddareddigari V, Ramalingam SS, Reddy SK, Eaby-Sandy B, Vavalà T, Whiteley A, Chen H, Yan Y, Sheehan JH, Meiler J, Morosini D, Ross JS, Stephens PJ, Miller VA, Ali SM, Lovly CM. EGFR Fusions as Novel Therapeutic Targets in Lung Cancer. Cancer Discov 2016; 6:601-11.
    • 4 Costa DB. Kinase inhibitor-responsive genotypes in EGFR mutated lung adenocarcinomas: moving past common point mutations or indels into uncommon kinase domain duplications and rearrangements. Transl Lung Cancer Res 2016; 5:331-7.
    • 4 Kuiper JL, Hashemi SM, Thunnissen E, Snijders PJ, Grünberg K, Bloemena E, Sie D, Postmus PE, Heideman DA, Smit EF. Non-classic EGFR mutations in a cohort of Dutch EGFR-mutated NSCLC patients and outcomes following EGFR-TKI treatment. Br J Cancer 2016; 115:1504-1512.
    • 4 Zhu YC, Wang WX, Xu CW, Song ZB, Du KQ, Chen G, Lv TF, Song Y. EGFR-RAD51 fusion variant in lung adenocarcinoma and response to erlotinib: A case report. Lung Cancer 2018; 115:131-134.
    • 4 Wang J, Li X, Xue X, Ou Q, Wu X, Liang Y, Wang X, You M, Shao YW, Zhang Z, Zhang S. Clinical outcomes of EGFR kinase domain duplication to targeted therapies in NSCLC. Int J Cancer 2019; 144:2677-2682.
    • 4 Ruiz-Patiño A, Castro CD, Ricaurte LM, Cardona AF, Rojas L, Zatarain-Barrón ZL, Wills B, Reguart N, Carranza H, Vargas C, Otero J, Corrales L, Martín C, Archila P, Rodriguez J, Avila J, Bravo M, Pino LE, Rosell R, Arrieta O; Latin-American Consortium for the Investigation of Lung Cancer (CLICaP). EGFR Amplification and Sensitizing Mutations Correlate with Survival in Lung Adenocarcinoma Patients Treated with Erlotinib (MutP-CLICaP). Target Oncol 2018; 13:621-629.
    • 4 Li Y, Zhang HB, Chen X, Yang X, Ye Y, Bekaii-Saab T, Zheng Y, Zhang Y. A Rare EGFR-SEPT14 Fusion in a Patient with Colorectal Adenocarcinoma Responding to Erlotinib. Oncologist 2020; 25:203-207.
    • 4 Peng X, Long X, Liu L, Zeng L, Yang H, Jiang W, Liao D, Li K, Wang J, Lizaso A, Mao X, Xu Q, Mansfield AS, Yang N, Zhang Y. Clinical impact of uncommon epidermal growth factor receptor exon 19 insertion-deletion variants on epidermal growth factor receptor-tyrosine kinase inhibitor efficacy in non-small-cell lung cancer. Eur J Cancer 2020; 141:199-208.
    • 4 Hirokawa E, Watanabe S, Sakai K, Takeda M, Sato C, Takahama T, Nishio K, Nakagawa K. Durable response to EGFR tyrosine kinase inhibitors in a patient with non-small cell lung cancer harboring an EGFR kinase domain duplication. Thorac Cancer 2021; 12:2283-2287.
    • 4 Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 2021; 597:732-737.
    • 4 Maron SB, Moya S, Morano F, Emmett MJ, Chou JF, Sabwa S, Walch H, Peterson B, Schrock AB, Zhang L, Janjigian YY, Chalasani S, Ku GY, Disel U, Enzinger P, Uboha N, Kato S, Yoshino T, Shitara K, Nakamura Y, Saeed A, Kasi P, Chao J, Lee J, Capanu M, Wainberg Z, Petty R, Pietrantonio F, Klempner SJ, Catenacci DVT. Epidermal Growth Factor Receptor Inhibition in Epidermal Growth Factor Receptor-Amplified Gastroesophageal Cancer: Retrospective Global Experience. J Clin Oncol 2022 Mar 29:JCO2102453. [Epub ahead of print]
    • Erlotinib + Osimertinib
    • EGFR
    • 4 Zhou Z, Zhao Y, Shen S, Gu L, Niu X, Xu Y, Zhang T, Xiang J, Mao X, Lu S. Durable Clinical Response of Lung Adenocarcinoma Harboring EGFR 19Del/T790M/in trans-C797S to Combination Therapy of First- and Third-Generation EGFR Tyrosine Kinase Inhibitors. J Thorac Oncol 2019; 14:e157-e159.
    • Everolimus
    • MTOR
    • R2 Wagle N, Grabiner BC, Van Allen EM, Amin-Mansour A, Taylor-Weiner A, Rosenberg M, Gray N, Barletta JA, Guo Y, Swanson SJ, Ruan DT, Hanna GJ, Haddad RI, Getz G, Kwiatkowski DJ, Carter SL, Sabatini DM, Jänne PA, Garraway LA, Lorch JH. Response and acquired resistance to everolimus in anaplastic thyroid cancer. N Engl J Med 2014; 371:1426-33.
    • PIK3CA, PTEN
    • R2 Kim ST, Lee J, Park SH, Park JO, Park YS, Kang WK, Lim HY. Prospective phase II trial of everolimus in PIK3CA amplification/mutation and/or PTEN loss patients with advanced solid tumors refractory to standard therapy. BMC Cancer 2017; 17:211.
    • TSC1, TSC2
    • 1 Franz DN, Belousova E, Sparagana S, Bebin EM, Frost M, Kuperman R, Witt O, Kohrman MH, Flamini JR, Wu JY, Curatolo P, de Vries PJ, Whittemore VH, Thiele EA, Ford JP, Shah G, Cauwel H, Lebwohl D, Sahmoud T, Jozwiak S. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 2013; 381:125-32.
    • 1 Krueger DA, Care MM, Agricola K, Tudor C, Mays M, Franz DN. Everolimus long-term safety and efficacy in subependymal giant cell astrocytoma. Neurology 2013; 80:574-80.
    • PTEN
    • 3 André F, Hurvitz S, Fasolo A, Tseng LM, Jerusalem G, Wilks S, O'Regan R, Isaacs C, Toi M, Burris H, He W, Robinson D, Riester M, Taran T, Chen D, Slamon D. Molecular Alterations and Everolimus Efficacy in Human Epidermal Growth Factor Receptor 2-Overexpressing Metastatic Breast Cancers: Combined Exploratory Biomarker Analysis From BOLERO-1 and BOLERO-3. J Clin Oncol 2016; 34:2115-24.
    • NF2
    • 4 Everolimus in Patients With Advanced Solid Malignancies With TSC1, TSC2, NF1, NF2, or STK11 Mutations [NCT02352844]
    • TSC2
    • 4 Wagner AJ, Malinowska-Kolodziej I, Morgan JA, Qin W, Fletcher CD, Vena N, Ligon AH, Antonescu CR, Ramaiya NH, Demetri GD, Kwiatkowski DJ, Maki RG. Clinical activity of mTOR inhibition with sirolimus in malignant perivascular epithelioid cell tumors: targeting the pathogenic activation of mTORC1 in tumors. J Clin Oncol 2010; 28:835-40.
    • 4 Italiano A, Delcambre C, Hostein I, Cazeau AL, Marty M, Avril A, Coindre JM, Bui B. Treatment with the mTOR inhibitor temsirolimus in patients with malignant PEComa. Ann Oncol 2010; 21:1135-7.
    • STK11
    • 4 Klümpen HJ, Queiroz KC, Spek CA, van Noesel CJ, Brink HC, de Leng WW, de Wilde RF, Mathus-Vliegen EM, Offerhaus GJ, Alleman MA, Westermann AM, Richel DJ. mTOR inhibitor treatment of pancreatic cancer in a patient With Peutz-Jeghers syndrome. J Clin Oncol 2011; 29:e150-3.
    • TSC2
    • 4 Dickson MA, Schwartz GK, Antonescu CR, Kwiatkowski DJ, Malinowska IA. Extrarenal perivascular epithelioid cell tumors (PEComas) respond to mTOR inhibition: clinical and molecular correlates. Int J Cancer 2013; 132:1711-7.
    • TSC1, TSC2
    • 4 Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Frost M, Belousova E, Sauter M, Nonomura N, Brakemeier S, de Vries PJ, Whittemore VH, Chen D, Sahmoud T, Shah G, Lincy J, Lebwohl D, Budde K. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 2013; 381:817-24.
    • MTOR
    • 4 Milowsky MI, Iyer G, Regazzi AM, Al-Ahmadie H, Gerst SR, Ostrovnaya I, Gellert LL, Kaplan R, Garcia-Grossman IR, Pendse D, Balar AV, Flaherty AM, Trout A, Solit DB, Bajorin DF. Phase II study of everolimus in metastatic urothelial cancer. BJU Int 2013; 112:462-70.
    • TSC2
    • 4 Wagle N, Grabiner BC, Van Allen EM, Amin-Mansour A, Taylor-Weiner A, Rosenberg M, Gray N, Barletta JA, Guo Y, Swanson SJ, Ruan DT, Hanna GJ, Haddad RI, Getz G, Kwiatkowski DJ, Carter SL, Sabatini DM, Jänne PA, Garraway LA, Lorch JH. Response and acquired resistance to everolimus in anaplastic thyroid cancer. N Engl J Med 2014; 371:1426-33.
    • MTOR, TSC1, TSC2
    • 4 Kwiatkowski DJ, Choueiri TK, Fay AP, Rini BI, Thorner AR, de Velasco G, Tyburczy ME, Hamieh L, Albiges L, Agarwal N, Ho TH, Song J, Pignon JC, Barrios PM, Michaelson MD, Van Allen E, Krajewski KM, Porta C, Pal S, Bellmunt J, McDermott DF, Heng DYC, Gray KP, Signoretti S. Mutations in TSC1, TSC2, and MTOR Are Associated with Response to Rapalogs in Patients with Metastatic Renal Cell Carcinoma. Clin Cancer Res 2016; 22:2445-2452.
    • STK11
    • 4 Donovan LE, Arnal AV, Wang SH, Odia Y. Widely metastatic atypical pituitary adenoma with mTOR pathway STK11(F298L) mutation treated with everolimus therapy. CNS Oncol 2016; 5:203-9.
    • PTEN, TSC1, TSC2
    • 4 Knox JJ, Barrios CH, Kim TM, Cosgriff T, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page RD, Beck JT, Cheung F, Yadav S, Patel P, Geoffrois L, Niolat J, Berkowitz N, Marker M, Chen D, Motzer RJ. Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC. Ann Oncol 2018; 29:2269.
    • FGFR1
    • 4 Drago JZ, Formisano L, Juric D, Niemierko A, Servetto A, Wander SA, Spring LM, Vidula N, Younger J, Peppercorn J, Yuen M, Malvarosa G, Sgroi D, Isakoff SJ, Moy B, Ellisen LW, Iafrate AJ, Arteaga CL, Bardia A. FGFR1 Amplification Mediates Endocrine Resistance but Retains TORC Sensitivity in Metastatic Hormone Receptor-Positive (HR+) Breast Cancer. Clin Cancer Res 2019; 25:6443-6451.
    • Everolimus + Docetaxel
    • NF2
    • 4 Ali SM, Miller VA, Ross JS, Pal SK. Exceptional Response on Addition of Everolimus to Taxane in Urothelial Carcinoma Bearing an NF2 Mutation. Eur Urol 2015; 67:1195-1196.
    • Everolimus + Letrozole
    • ESR1
    • 3 van Weelden WJ, Massuger LFAG; ENITEC, Pijnenborg JMA, Romano A. Anti-estrogen Treatment in Endometrial Cancer: A Systematic Review. Front Oncol 2019; 9:359. eCollection 2019.
    • Everolimus + Trastuzumab
    • PTEN+ERBB2
    • 3 André F, O'Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, Masuda N, Wilks S, Arena F, Isaacs C, Yap YS, Papai Z, Lang I, Armstrong A, Lerzo G, White M, Shen K, Litton J, Chen D, Zhang Y, Ali S, Taran T, Gianni L. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol 2014; 15:580-91.
    • Exemestane
    • ESR1
    • R2 Jeselsohn R, Buchwalter G, De Angelis C, Brown M, Schiff R. ESR1 mutations—a mechanism for acquired endocrine resistance in breast cancer. Nat Rev Clin Oncol 2015; 12:573-83.
    • PGR
    • 1 McGuire WL, Horwitz KB, Pearson OH, Segaloff A. Current status of estrogen and progesterone receptors in breast cancer. Cancer 1977; 39(6 Suppl):2934-47.
    • 1 Kiang DT, Kennedy BJ. Tamoxifen (antiestrogen) therapy in advanced breast cancer. Ann Intern Med 1977; 87:687-90.
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    • 1 Muss HB, Wells HB, Paschold EH, Black WR, Cooper MR, Capizzi RL, Christian R, Cruz JM, Jackson DV, Powell BL, et al. Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association. J Clin Oncol 1988; 6:1098-106.
    • 1 Stuart NS, Warwick J, Blackledge GR, Spooner D, Keen C, Taylor AR, Tyrell C, Webster DJ, Earl H. A randomised phase III cross-over study of tamoxifen versus megestrol acetate in advanced and recurrent breast cancer. Eur J Cancer 1996; 32A:1888-92.
    • 1 Taylor CW, Green S, Dalton WS, Martino S, Rector D, Ingle JN, Robert NJ, Budd GT, Paradelo JC, Natale RB, Bearden JD, Mailliard JA, Osborne CK. Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer: an intergroup study. J Clin Oncol 1998; 16:994-9.
    • ESR1, PGR
    • 1 The Exemestane Study Group. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial.. J Clin Oncol 2000; 18:1399-411.
    • PGR
    • 1 Mouridsen H, Gershanovich M, Sun Y, Pérez-Carrión R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Jänicke F, Pluzanska A, Dank M, Becquart D, Bapsy PP, Salminen E, Snyder R, Lassus M, Verbeek JA, Staffler B, Chaudri-Ross HA, Dugan M. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 2001; 19:2596-606.
    • 1 Bonneterre J, Buzdar A, Nabholtz JM, Robertson JF, Thürlimann B, von Euler M, Sahmoud T, Webster A, Steinberg M; Arimidex Writing Committee; Investigators Committee Members. Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma. Cancer 2001; 92:2247-58.
    • ESR1
    • 3 van Weelden WJ, Massuger LFAG; ENITEC, Pijnenborg JMA, Romano A. Anti-estrogen Treatment in Endometrial Cancer: A Systematic Review. Front Oncol 2019; 9:359. eCollection 2019.
    • eFT508
    • MYD88
    • 4 Kevin R. Webster, Vikas K Goel, Ivy NJ Hung, Gregory S Parker, Jocelyn Staunton, Melissa Neal, Jolene Molter, Gary G Chiang, Katti A. Jessen, Christopher J Wegerski, Samuel Sperry, Vera Huang, Joan Chen, Peggy A Thompson, James R Appleman, Stephen E Webber, Paul A Sprengeler, Siegfried H Reich; eFT508, a Potent and Selective Mitogen-Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 Inhibitor, Is Efficacious in Preclinical Models of Diffuse Large B-Cell Lymphoma (DLBCL). Blood 2015; 126 (23): 1554. doi: https://doi.org/10.1182/blood.V126.23.1554.1554
    • F
    • FCN-159
    • NF1
    • 4 Hu X, Zeng K, Xu Z, Li W, Li C, Kang Z, Li S, Hui A, Wu Z, Huang X, Han P, Li B, Lin X. A multicenter, open-label, single-arm, phase 1 dose-escalation study to evaluate the safety, tolerability, and anti-tumor activity of FCN-159 in adults with neurofibromatosis type 1. J Clin Oncol 2022; 40(16_suppl): 3011-3011.
    • FOLFIRI + Cetuximab
    • KRAS+NRAS
    • 1 Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009; 360:1408-17.
    • EGFR
    • 4 Maron SB, Alpert L, Kwak HA, Lomnicki S, Chase L, Xu D, O'Day E, Nagy RJ, Lanman RB, Cecchi F, Hembrough T, Schrock A, Hart J, Xiao SY, Setia N, Catenacci DVT. Targeted Therapies for Targeted Populations: Anti-EGFR Treatment for EGFR-Amplified Gastroesophageal Adenocarcinoma. Cancer Discov 2018; 8:696-713.
    • Consensus molecular subtype
    • 4 Stintzing S, Wirapati P, Lenz HJ, Neureiter D, Fischer von Weikersthal L, Decker T, Kiani A, Kaiser F, Al-Batran S, Heintges T, Lerchenmüller C, Kahl C, Seipelt G, Kullmann F, Moehler M, Scheithauer W, Held S, Modest DP, Jung A, Kirchner T, Aderka D, Tejpar S, Heinemann V. Consensus molecular subgroups (CMS) of colorectal cancer (CRC) and first-line efficacy of FOLFIRI plus cetuximab or bevacizumab in the FIRE3 (AIO KRK-0306) trial. Ann Oncol 2019; 30:1796-1803.
    • FOLFIRINOX
    • RAD51C
    • 4 Palacio S, Pollack T, Silva-Smith R, Sussman DA, Hosein PJ. Exceptional response to FOLFIRINOX in a patient with pancreatic cancer and a germline RAD51C mutation. J Gastrointest Oncol 2018; 9:E19-E22.
    • PALB2
    • 4 Wattenberg MM, Asch D, Yu S, O'Dwyer PJ, Domchek SM, Nathanson KL, Rosen MA, Beatty GL, Siegelman ES, Reiss KA. Platinum response characteristics of patients with pancreatic ductal adenocarcinoma and a germline BRCA1, BRCA2 or PALB2 mutation. Br J Cancer 2020; 122:333-339.
    • FOLFOX + ABT-806
    • EGFR
    • 4 Maron SB, Alpert L, Kwak HA, Lomnicki S, Chase L, Xu D, O'Day E, Nagy RJ, Lanman RB, Cecchi F, Hembrough T, Schrock A, Hart J, Xiao SY, Setia N, Catenacci DVT. Targeted Therapies for Targeted Populations: Anti-EGFR Treatment for EGFR-Amplified Gastroesophageal Adenocarcinoma. Cancer Discov 2018; 8:696-713.
    • FOLFOX + Panitumumab
    • KRAS, NRAS
    • R1 Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008; 359:1757-65.
    • BRAF
    • R1 De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F, Rougier P, Vincenzi B, Santini D, Tonini G, Cappuzzo F, Frattini M, Molinari F, Saletti P, De Dosso S, Martini M, Bardelli A, Siena S, Sartore-Bianchi A, Tabernero J, Macarulla T, Di Fiore F, Gangloff AO, Ciardiello F, Pfeiffer P, Qvortrup C, Hansen TP, Van Cutsem E, Piessevaux H, Lambrechts D, Delorenzi M, Tejpar S. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol 2010; 11:753-62.
    • KRAS, NRAS
    • R1 Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 2013; 369:1023-34.
    • HRAS
    • R2 Boidot R, Chevrier S, Julie V, Ladoire S, Ghiringhelli F. HRAS G13D, a new mutation implicated in the resistance to anti-EGFR therapies in colorectal cancer, a case report. Int J Colorectal Dis 2016; 31:1245-6.
    • KRAS+NRAS
    • 1 . . [DOI:]
    • FOLFOXIRI + Bevacizumab + Atezolizumab
    • Immunoscore IC, Mismatch repair, Tumour Mutational Burden
    • Fadraciclib
    • CCNE1, MCL1
    • 4 Do K, Frej K, Bhushan K, Pruitt-Thompson S, Zheleva D, Blake D, Chiao J, Shapiro G. Phase 1 safety, pharmacokinetic and pharmacodynamic study of fadraciclib (CYC065), a cyclin dependent kinase inhibitor, in patients with advanced cancers (NCT02552953). E J Cancer 2020; 138 (2): S7. 10.1016/S0959-8049(20)31086-8
    • Fam-trastuzumab deruxtecan-nxki
    • ERBB2
    • 1B Cortés J, Kim S, Chung W, Im S, Park Y, Hegg R, Kim M, Tseng L, Petry V, Chung C, Iwata H, Hamilton E, Curigliano G, Xu B, Lee C, Liu Y, Cathcart J, Bako E, Verma S, Hurvitz S. LBA1 Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (Pts) with HER2+ metastatic breast cancer (mBC): Results of the randomized phase III DESTINY-Breast03 study. Ann Oncol 2021; 32 (5): S1287. 10.1016/j.annonc.2021.08.2087
    • 1B Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, Andre F, Iwata H, Ito Y, Tsurutani J, Sohn J, Denduluri N, Perrin C, Aogi K, Tokunaga E, Im SA, Lee KS, Hurvitz SA, Cortes J, Lee C, Chen S, Zhang L, Shahidi J, Yver A, Krop I; DESTINY-Breast01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med 2020; 382:610-621.
    • ERBB2
    • R2 Siena S, Bartolomeo MD, Raghav KPS, Masuishi T, Loupakis F, Kawakami H, Yamaguchi K, Nishina T, Fakih M, Elez E, Rodriguez J, Ciardiello F, Saxena K, Yamamoto E, Bako E, Okuda Y, Shahidi J, Grothey A, Yoshino T, Japan WCCGTNCCHEK. A phase II, multicenter, open-label study of trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): DESTINY-CRC01. J Clin Oncol 2020; 38(15_suppl): 4000-4000.
    • R2 Siena S, Di Bartolomeo M, Raghav K, Masuishi T, Loupakis F, Kawakami H, Yamaguchi K, Nishina T, Fakih M, Elez E, Rodriguez J, Ciardiello F, Komatsu Y, Esaki T, Chung K, Wainberg Z, Sartore-Bianchi A, Saxena K, Yamamoto E, Bako E, Okuda Y, Shahidi J, Grothey A, Yoshino T; DESTINY-CRC01 investigators. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial. Lancet Oncol 2021; 22:779-789.
    • ERBB2
    • 2 Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med 2020; 382:2419-2430.
    • 2 Li BT, Smit EF, Goto Y, Nakagawa K, Udagawa H, Mazières J, Nagasaka M, Bazhenova L, Saltos AN, Felip E, Pacheco JM, Pérol M, Paz-Ares L, Saxena K, Shiga R, Cheng Y, Acharyya S, Vitazka P, Shahidi J, Planchard D, Jänne PA; DESTINY-Lung01 Trial Investigators. Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med 2021 Sep 18. [Epub ahead of print]
    • 2 Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med 2022 Jun 5. [Epub ahead of print]
    • ERBB2+KRAS
    • 3 Siena S, Bartolomeo MD, Raghav KPS, Masuishi T, Loupakis F, Kawakami H, Yamaguchi K, Nishina T, Fakih M, Elez E, Rodriguez J, Ciardiello F, Saxena K, Yamamoto E, Bako E, Okuda Y, Shahidi J, Grothey A, Yoshino T, Japan WCCGTNCCHEK. A phase II, multicenter, open-label study of trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): DESTINY-CRC01. J Clin Oncol 2020; 38(15_suppl): 4000-4000.
    • ERBB2
    • 3 Smit EF, Nakagawa K, Nagasaka M, Felip E, Goto Y, Li BT, Pacheco JM, Murakami H, Barlesi F, Saltos AN, Perol M, Udagawa H, Saxena K, Shiga R, Guevara FM, Acharyya S, Shahidi J, Planchard D, Janne PA. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): Interim results of DESTINY-Lung01. J Clin Oncol 2020; 38(15_suppl): 9504-9504.
    • ERBB2+KRAS
    • 3 Yoshino T, Bartolomeo MD, Raghav KPS, Masuishi T, Loupakis F, Kawakami H, Yamaguchi K, Nishina T, Wainberg ZA, Elez E, Rodriguez J, Fakih M, Ciardiello F, Saxena K, Kobayashi K, Bako E, Okuda Y, Meinhardt G, Grothey A, Siena S, Center , Niguarda GOM, Milan , Italy . Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): Final results from a phase 2, multicenter, open-label study (DESTINY-CRC01). J Clin Oncol 2021; 39(15_suppl): 3505-3505.
    • ERBB2
    • 3 . . [DOI:]
    • ERBB2+KRAS
    • 3 Siena S, Di Bartolomeo M, Raghav K, Masuishi T, Loupakis F, Kawakami H, Yamaguchi K, Nishina T, Fakih M, Elez E, Rodriguez J, Ciardiello F, Komatsu Y, Esaki T, Chung K, Wainberg Z, Sartore-Bianchi A, Saxena K, Yamamoto E, Bako E, Okuda Y, Shahidi J, Grothey A, Yoshino T; DESTINY-CRC01 investigators. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial. Lancet Oncol 2021; 22:779-789.
    • ERBB2
    • 4 Smit EF, Nakagawa K, Nagasaka M, Felip E, Goto Y, Li BT, Pacheco JM, Murakami H, Barlesi F, Saltos AN, Perol M, Udagawa H, Saxena K, Shiga R, Guevara FM, Acharyya S, Shahidi J, Planchard D, Janne PA. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): Interim results of DESTINY-Lung01. J Clin Oncol 2020; 38(15_suppl): 9504-9504.
    • 4 . . [DOI:]
    • 4 Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, Andre F, Iwata H, Ito Y, Tsurutani J, Sohn J, Denduluri N, Perrin C, Aogi K, Tokunaga E, Im SA, Lee KS, Hurvitz SA, Cortes J, Lee C, Chen S, Zhang L, Shahidi J, Yver A, Krop I; DESTINY-Breast01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med 2020; 382:610-621.
    • 4 Modi S, Park H, Murthy RK, Iwata H, Tamura K, Tsurutani J, Moreno-Aspitia A, Doi T, Sagara Y, Redfern C, Krop IE, Lee C, Fujisaki Y, Sugihara M, Zhang L, Shahidi J, Takahashi S. Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low-Expressing Advanced Breast Cancer: Results From a Phase Ib Study. J Clin Oncol 2020; 38:1887-1896.
    • Famitinib + Camrelizumab + Nab-paclitaxel
    • Tumour microenvironment
    • 3 Chen L, Zhimin S, Wang Z, Yang W, Jiang Y, Zou J, Wu J, Di G, Liu G, Yu K, Fan L, Li J, Hou Y, Hu Z, Chen C, Huang X, Cao A, Hu X, Wu S, Zhao S. Combination of famitinib with camrelizumab plus nab-paclitaxel as first-line treatment for patients with immunomodulatory advanced triple-negative breast cancer (FUTURE-C-PLUS): A prospective, single-arm, phase 2 study. J Clin Oncol 2021; 39(15_suppl): 1007-1007.
    • Fedratinib
    • JAK2
    • 2 Harrison CN, Schaap N, Vannucchi AM, Kiladjian JJ, Tiu RV, Zachee P, Jourdan E, Winton E, Silver RT, Schouten HC, Passamonti F, Zweegman S, Talpaz M, Lager J, Shun Z, Mesa RA. Janus kinase-2 inhibitor fedratinib in patients with myelofibrosis previously treated with ruxolitinib (JAKARTA-2): a single-arm, open-label, non-randomised, phase 2, multicentre study. Lancet Haematol 2017; 4:e317-e324.
    • Fisogatinib
    • FGFR4
    • R2 Hatlen MA, Schmidt-Kittler O, Sherwin CA, Rozsahegyi E, Rubin N, Sheets MP, Kim JL, Miduturu C, Bifulco N, Brooijmans N, Shi H, Guzi T, Boral A, Lengauer C, Dorsch M, Kim RD, Kang YK, Wolf BB, Hoeflich KP. Acquired On-Target Clinical Resistance Validates FGFR4 as a Driver of Hepatocellular Carcinoma. Cancer Discov 2019; 9:1686-1695.
    • FGF19
    • 4 Hatlen MA, Schmidt-Kittler O, Sherwin CA, Rozsahegyi E, Rubin N, Sheets MP, Kim JL, Miduturu C, Bifulco N, Brooijmans N, Shi H, Guzi T, Boral A, Lengauer C, Dorsch M, Kim RD, Kang YK, Wolf BB, Hoeflich KP. Acquired On-Target Clinical Resistance Validates FGFR4 as a Driver of Hepatocellular Carcinoma. Cancer Discov 2019; 9:1686-1695.
    • Flutamide
    • AR
    • R2 Lallous N, Volik SV, Awrey S, Leblanc E, Tse R, Murillo J, Singh K, Azad AA, Wyatt AW, LeBihan S, Chi KN, Gleave ME, Rennie PS, Collins CC, Cherkasov A. Functional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients. Genome Biol 2016; 17:10.
    • Foretinib
    • CDH1
    • 4 Bajrami I, Marlow R, van de Ven M, Brough R, Pemberton HN, Frankum J, Song F, Rafiq R, Konde A, Krastev DB, Menon M, Campbell J, Gulati A, Kumar R, Pettitt SJ, Gurden MD, Cardenosa ML, Chong I, Gazinska P, Wallberg F, Sawyer EJ, Martin LA, Dowsett M, Linardopoulos S, Natrajan R, Ryan CJ, Derksen PWB, Jonkers J, Tutt ANJ, Ashworth A, Lord CJ. E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer. Cancer Discov 2018; 8:498-515.
    • Fulvestrant
    • ESR1
    • R2 Kingston B, Pearson A, Herrera-Abreu MT, Cutts R, Moretti L, Kilburn L, Johnson H, MacPherson IR, Ring AE, Bliss J, Katzenellenbogen JA, Turner NC. ESR1 F404 mutations and acquired resistance to fulvestrant in the plasmaMATCH study. J Clin Oncol 2022; 40(16_suppl): 1009-1009.
    • ARID1A
    • R2 Xu G, Chhangawala S, Cocco E, Razavi P, Cai Y, Otto JE, Ferrando L, Selenica P, Ladewig E, Chan C, Da Cruz Paula A, Witkin M, Cheng Y, Park J, Serna-Tamayo C, Zhao H, Wu F, Sallaku M, Qu X, Zhao A, Collings CK, D'Avino AR, Jhaveri K, Koche R, Levine RL, Reis-Filho JS, Kadoch C, Scaltriti M, Leslie CS, Baselga J, Toska E. ARID1A determines luminal identity and therapeutic response in estrogen-receptor-positive breast cancer. Nat Genet 2020; 52:198-207.
    • ESR1
    • 1 Robertson JFR, Bondarenko IM, Trishkina E, Dvorkin M, Panasci L, Manikhas A, Shparyk Y, Cardona-Huerta S, Cheung KL, Philco-Salas MJ, Ruiz-Borrego M, Shao Z, Noguchi S, Rowbottom J, Stuart M, Grinsted LM, Fazal M, Ellis MJ. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet 2016; 388:2997-3005.
    • ESR1
    • 3 van Weelden WJ, Massuger LFAG; ENITEC, Pijnenborg JMA, Romano A. Anti-estrogen Treatment in Endometrial Cancer: A Systematic Review. Front Oncol 2019; 9:359. eCollection 2019.
    • Fulvestrant + Alpelisib
    • PIK3CA
    • 1B André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, Iwata H, Conte P, Mayer IA, Kaufman B, Yamashita T, Lu YS, Inoue K, Takahashi M, Pápai Z, Longin AS, Mills D, Wilke C, Hirawat S, Juric D; SOLAR-1 Study Group. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med 2019; 380:1929-1940.
    • PIK3CA+FGFR1, PIK3CA+FGFR2
    • 3 Juric D, Rugo HS, Reising A, Ma C, Ciruelos EM, Loibl S, Singer CF, Sohn J, Campone M, Conte P, Iwata H, Ghaznawi F, Miller MK, Taran T, Su F, Andre F. Alpelisib (ALP) + fulvestrant (FUL) in patients (pts) with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (ABC): Biomarker (BM) analyses by next-generation sequencing (NGS) from the SOLAR-1 study. J Clin Oncol 2022; 40(16_suppl): 1006-1006.
    • Fulvestrant + Copanlisib
    • PIK3CA
    • 4 Study of a New Drug Combination, Copanlisib and Fulvestrant, in Postmenopausal Women With Advanced Breast Cancer [NCT03803761]
    • Fulvestrant + Neratinib
    • ERBB2
    • R2 Smyth LM, Piha-Paul SA, Won HH, Schram AM, Saura C, Loi S, Lu J, Shapiro GI, Juric D, Mayer IA, Arteaga CL, de la Fuente MI, Brufksy AM, Spanggaard I, Mau-Sørensen M, Arnedos M, Moreno V, Boni V, Sohn J, Schwartzberg LS, Gonzàlez-Farré X, Cervantes A, Bidard FC, Gorelick AN, Lanman RB, Nagy RJ, Ulaner GA, Chandarlapaty S, Jhaveri K, Gavrila EI, Zimel C, Selcuklu SD, Melcer M, Samoila A, Cai Y, Scaltriti M, Mann G, Xu F, Eli LD, Dujka M, Lalani AS, Bryce R, Baselga J, Taylor BS, Solit DB, Meric-Bernstam F, Hyman DM. Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer. Cancer Discov 2020; 10:198-213.
    • ERBB2
    • 3 Smyth LM, Piha-Paul SA, Won HH, Schram AM, Saura C, Loi S, Lu J, Shapiro GI, Juric D, Mayer IA, Arteaga CL, de la Fuente MI, Brufksy AM, Spanggaard I, Mau-Sørensen M, Arnedos M, Moreno V, Boni V, Sohn J, Schwartzberg LS, Gonzàlez-Farré X, Cervantes A, Bidard FC, Gorelick AN, Lanman RB, Nagy RJ, Ulaner GA, Chandarlapaty S, Jhaveri K, Gavrila EI, Zimel C, Selcuklu SD, Melcer M, Samoila A, Cai Y, Scaltriti M, Mann G, Xu F, Eli LD, Dujka M, Lalani AS, Bryce R, Baselga J, Taylor BS, Solit DB, Meric-Bernstam F, Hyman DM. Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer. Cancer Discov 2020; 10:198-213.
    • Fulvestrant + Palbociclib
    • CCNE1
    • R2 Pascual J, Gil-Gil M, Zielinski C, Hills M, Ruiz-Borrego M, Ciruelos EM, Garcia-Murillas I, Muñoz M, Bermejo B, Swift C, Vila MM, Torres AA, Nissenbaum B, Murillo L, Liu Y, Herranz J, Caballero R, Guerrero-Zotano A, Turner NC, Martin M, Group TiPGBC, Badalona , Group SHUMSGBC, Zaragoza , Oncology SCCEC, Wien , Jorge AHGUS, Group GBC, Huesca , Inc SP, Diego S, Group CGBC, Madrid , Oncología SIVd, Group GBC, Valencia , Trust STRMNF, London , Marañón UKIdISG, CIBERONC , Group UCdMGBC, Madrid , Spain . CCNE1 mRNA and cyclin E1 protein expression as predictive biomarkers for efficacy of palbociclib plus fulvestrant versus capecitabine in the phase III PEARL study. J Clin Oncol 2021; 39(15_suppl): 1014-1014.
    • FGFR1
    • R2 Formisano L, Lu Y, Servetto A, Hanker AB, Jansen VM, Bauer JA, Sudhan DR, Guerrero-Zotano AL, Croessmann S, Guo Y, Ericsson PG, Lee KM, Nixon MJ, Schwarz LJ, Sanders ME, Dugger TC, Cruz MR, Behdad A, Cristofanilli M, Bardia A, O'Shaughnessy J, Nagy RJ, Lanman RB, Solovieff N, He W, Miller M, Su F, Shyr Y, Mayer IA, Balko JM, Arteaga CL. Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer. Nat Commun 2019; 10:1373.
    • R2 Drago JZ, Formisano L, Juric D, Niemierko A, Servetto A, Wander SA, Spring LM, Vidula N, Younger J, Peppercorn J, Yuen M, Malvarosa G, Sgroi D, Isakoff SJ, Moy B, Ellisen LW, Iafrate AJ, Arteaga CL, Bardia A. FGFR1 Amplification Mediates Endocrine Resistance but Retains TORC Sensitivity in Metastatic Hormone Receptor-Positive (HR+) Breast Cancer. Clin Cancer Res 2019; 25:6443-6451.
    • Fulvestrant + Palbociclib + Erdafitinib
    • FGFR1
    • 4 Formisano L, Lu Y, Servetto A, Hanker AB, Jansen VM, Bauer JA, Sudhan DR, Guerrero-Zotano AL, Croessmann S, Guo Y, Ericsson PG, Lee KM, Nixon MJ, Schwarz LJ, Sanders ME, Dugger TC, Cruz MR, Behdad A, Cristofanilli M, Bardia A, O'Shaughnessy J, Nagy RJ, Lanman RB, Solovieff N, He W, Miller M, Su F, Shyr Y, Mayer IA, Balko JM, Arteaga CL. Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer. Nat Commun 2019; 10:1373.
    • Fulvestrant + Ribociclib
    • FGFR1, FGFR2
    • R2 Formisano L, Lu Y, Servetto A, Hanker AB, Jansen VM, Bauer JA, Sudhan DR, Guerrero-Zotano AL, Croessmann S, Guo Y, Ericsson PG, Lee KM, Nixon MJ, Schwarz LJ, Sanders ME, Dugger TC, Cruz MR, Behdad A, Cristofanilli M, Bardia A, O'Shaughnessy J, Nagy RJ, Lanman RB, Solovieff N, He W, Miller M, Su F, Shyr Y, Mayer IA, Balko JM, Arteaga CL. Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer. Nat Commun 2019; 10:1373.
    • FGFR1
    • R2 Drago JZ, Formisano L, Juric D, Niemierko A, Servetto A, Wander SA, Spring LM, Vidula N, Younger J, Peppercorn J, Yuen M, Malvarosa G, Sgroi D, Isakoff SJ, Moy B, Ellisen LW, Iafrate AJ, Arteaga CL, Bardia A. FGFR1 Amplification Mediates Endocrine Resistance but Retains TORC Sensitivity in Metastatic Hormone Receptor-Positive (HR+) Breast Cancer. Clin Cancer Res 2019; 25:6443-6451.
    • Futibatinib
    • FGFR2
    • R2 Goyal L, Baiev I, Zhang K, Dalgai S, Shroff R, Kelley R, Uboha N. Acquired resistance to selective FGFR inhibitors in FGFR-altered cholangiocarcinoma. E J Cancer 2020; 138 (2): S21. 10.1016/S0959-8049(20)31121-7
    • FGFR2
    • 3 Goyal L, Meric-Bernstam F, Hollebecque A, Valle JW, Morizane C, Karasic TB, Abrams TA, Furuse J, He Y, Soni N, Benhadji KA, Bridgewater JA. FOENIX-CCA2: A phase II, open-label, multicenter study of futibatinib in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 gene fusions or other rearrangements. J Clin Oncol 2020; 38(15_suppl): 108-108.
    • 3 . . [DOI:]
    • 3 Meric-Bernstam F, Bahleda R, Hierro C, Sanson M, Bridgewater J, Arkenau HT, Tran B, Kelley RK, Park JO, Javle M, He Y, Benhadji KA, Goyal L. Futibatinib, an Irreversible FGFR1-4 Inhibitor, in Patients with Advanced Solid Tumors Harboring FGF/FGFR Aberrations: A Phase I Dose-Expansion Study. Cancer Discov 2022; 12:402-415.
    • FGFR1, FGFR2
    • 4 Bahleda R, Meric-Bernstam F, Goyal L, Tran B, He Y, Yamamiya I, Benhadji KA, Matos I, Arkenau HT. Phase I, first-in-human study of futibatinib, a highly selective, irreversible FGFR1-4 inhibitor in patients with advanced solid tumors. Ann Oncol 2020; 31:1405-1412.
    • FGFR2
    • 4 Sootome H, Fujita H, Ito K, Ochiiwa H, Fujioka Y, Ito K, Miura A, Sagara T, Ito S, Ohsawa H, Otsuki S, Funabashi K, Yashiro M, Matsuo K, Yonekura K, Hirai H. Futibatinib Is a Novel Irreversible FGFR 1-4 Inhibitor That Shows Selective Antitumor Activity against FGFR-Deregulated Tumors. Cancer Res 2020; 80:4986-4997.
    • FGFR1, FGFR2, FGFR3
    • 4 Meric-Bernstam F, Bahleda R, Hierro C, Sanson M, Bridgewater J, Arkenau HT, Tran B, Kelley RK, Park JO, Javle M, He Y, Benhadji KA, Goyal L. Futibatinib, an Irreversible FGFR1-4 Inhibitor, in Patients with Advanced Solid Tumors Harboring FGF/FGFR Aberrations: A Phase I Dose-Expansion Study. Cancer Discov 2022; 12:402-415.
    • G
    • GDC-0077
    • PIK3CA
    • 4 Dejan Juric, Kevin Kalinsky, Mafalda Oliveira, Andres Cervantes, Philippe Bedard, Ian Krop, Erika Hamilton, Peter Schmid, Andrea Varga, Nick Turner, Antoine Italiano, Cristina Saura, Valentina Gambardella, Zachary Veitch, Leslie Dickmann, Naoki Kotani, Jill Fredrickson, Amy Kapp, Katie Hutchinson, Stephanie Royer-Joo, Anjali Vaze, Jennifer Schutzman, Komal Jhaveri. A first-in-human phase Ia dose escalation study of GDC-0077, a p110a-selective and mutant-degrading PI3K inhibitor, in patients with PIK3CA-mutant solid tumors [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-08-04.
    • GGTI-2418
    • KRAS
    • 4 Karasic TB, Chiorean EG, Sebti SM, O'Dwyer PJ. A Phase I Study of GGTI-2418 (Geranylgeranyl Transferase I Inhibitor) in Patients with Advanced Solid Tumors. Target Oncol 2019; 14:613-618.
    • GQ1001
    • ERBB2
    • 4 Safety of GQ1001 in Adult Patients With HER2-Positive Advanced Solid Tumors [NCT04450732]
    • GSK126
    • ARID1A
    • 4 Bitler BG, Aird KM, Garipov A, Li H, Amatangelo M, Kossenkov AV, Schultz DC, Liu Q, Shih IeM, Conejo-Garcia JR, Speicher DW, Zhang R. Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers. Nat Med 2015; 21:231-8.
    • GSK2256098
    • NF2
    • 3 Brastianos PK, Twohy E, Gerstner ER, Kaufmann TJ, Iafrate AJ, Jeyapalan SA, Piccioni DE, Lassman AB, Fadul CE, Schiff D, Taylor JW, Chowdhary SA, Kaley TJ, Morrison T, Kumthekar P, Geyer S, Cahill DP, Santagata S, Barker FG, Galanis E. Alliance A071401: Phase II trial of FAK inhibition in meningiomas with somatic NF2 mutations. J Clin Oncol 2020; 38(15_suppl): 2502-2502.
    • GSK2636771
    • PTEN
    • R2 Janku F, Jegede O, Puhalla S, Konstantinopoulos P, Meric-Bernstam F, Mitchell E, Zwiebel J, McShane L, Li S, Rubinstein L, Doyle L, Patton D, Conley B, O’Dwyer P, Harris L, Arteaga C, Williams P, Hamilton S, Chen A, Flaherty K. NCI-MATCH Arms N & P: Phase II study of PI3K beta inhibitor GSK2636771 in patients (pts) with cancers (ca) with PTEN mutation/deletion (mut/del) or PTEN protein loss. Ann Oncol 2018; 29 (8): . 10.1093/annonc/mdy279.406
    • PTEN
    • 3 Jung M, Kim C, Kim H, Lee C, Lee H, Bae W, Jeung H, Zang D, Park S, Hwang I, Kim H, Rha S, Chung H. SO-10 An open-label, multi-centre, phase Ib/II study of PI3Kβ selective inhibitor GSK2636771 administered in combination with paclitaxel in patients with advanced gastric cancer having alterations in PI3K/Akt pathway. Ann Oncol 2021; 32 (3): S206. 10.1016/j.annonc.2021.05.034
    • GSK2849330
    • ERBB3, NRG1
    • 4 Gan HK, Millward M, Jalving M, Garrido-Laguna I, Lickliter JD, Schellens JHM, Lolkema MP, Van Herpen CLM, Hug B, Tang L, O'Connor-Semmes R, Gagnon R, Ellis C, Ganji G, Matheny C, Drilon A. A Phase I, First-in-Human Study of GSK2849330, an Anti-HER3 Monoclonal Antibody, in HER3-Expressing Solid Tumors. Oncologist 2021; 26:e1844-e1853.
    • GSK3368715
    • MTAP
    • 4 Fedoriw A, Rajapurkar SR, O'Brien S, Gerhart SV, Mitchell LH, Adams ND, Rioux N, Lingaraj T, Ribich SA, Pappalardi MB, Shah N, Laraio J, Liu Y, Butticello M, Carpenter CL, Creasy C, Korenchuk S, McCabe MT, McHugh CF, Nagarajan R, Wagner C, Zappacosta F, Annan R, Concha NO, Thomas RA, Hart TK, Smith JJ, Copeland RA, Moyer MP, Campbell J, Stickland K, Mills J, Jacques-O'Hagan S, Allain C, Johnston D, Raimondi A, Porter Scott M, Waters N, Swinger K, Boriack-Sjodin A, Riera T, Shapiro G, Chesworth R, Prinjha RK, Kruger RG, Barbash O, Mohammad HP. Anti-tumor Activity of the Type I PRMT Inhibitor, GSK3368715, Synergizes with PRMT5 Inhibition through MTAP Loss. Cancer Cell 2019; 36:100-114.e25.
    • GSK343
    • H3F3A
    • 4 Mohammad F, Weissmann S, Leblanc B, Pandey DP, Højfeldt JW, Comet I, Zheng C, Johansen JV, Rapin N, Porse BT, Tvardovskiy A, Jensen ON, Olaciregui NG, Lavarino C, Suñol M, de Torres C, Mora J, Carcaboso AM, Helin K. EZH2 is a potential therapeutic target for H3K27M-mutant pediatric gliomas. Nat Med 2017; 23:483-492.
    • KDM6A
    • 4 Ezponda T, Dupéré-Richer D, Will CM, Small EC, Varghese N, Patel T, Nabet B, Popovic R, Oyer J, Bulic M, Zheng Y, Huang X, Shah MY, Maji S, Riva A, Occhionorelli M, Tonon G, Kelleher N, Keats J, Licht JD. UTX/KDM6A Loss Enhances the Malignant Phenotype of Multiple Myeloma and Sensitizes Cells to EZH2 inhibition. Cell Rep 2017; 21:628-640.
    • Gefitinib
    • EGFR
    • R1 Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong KK, Meyerson M, Eck MJ. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A 2008; 105:2070-5.
    • R1 Yasuda H, Kobayashi S, Costa DB. EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications. Lancet Oncol 2012; 13:e23-31.
    • EGFR
    • R2 Balak MN, Gong Y, Riely GJ, Somwar R, Li AR, Zakowski MF, Chiang A, Yang G, Ouerfelli O, Kris MG, Ladanyi M, Miller VA, Pao W. Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res 2006; 12:6494-501.
    • R2 Costa DB, Nguyen KS, Cho BC, Sequist LV, Jackman DM, Riely GJ, Yeap BY, Halmos B, Kim JH, Jänne PA, Huberman MS, Pao W, Tenen DG, Kobayashi S. Effects of erlotinib in EGFR mutated non-small cell lung cancers with resistance to gefitinib. Clin Cancer Res 2008; 14:7060-7.
    • R2 Uhm JH, Ballman KV, Wu W, Giannini C, Krauss JC, Buckner JC, James CD, Scheithauer BW, Behrens RJ, Flynn PJ, Schaefer PL, Dakhill SR, Jaeckle KA. Phase II evaluation of gefitinib in patients with newly diagnosed Grade 4 astrocytoma: Mayo/North Central Cancer Treatment Group Study N0074. Int J Radiat Oncol Biol Phys 2011; 80:347-53.
    • R2 Wu JY, Yu CJ, Chang YC, Yang CH, Shih JY, Yang PC. Effectiveness of tyrosine kinase inhibitors on "uncommon" epidermal growth factor receptor mutations of unknown clinical significance in non-small cell lung cancer. Clin Cancer Res 2011; 17:3812-21.
    • BCL2L11
    • R2 Ng KP, Hillmer AM, Chuah CT, Juan WC, Ko TK, Teo AS, Ariyaratne PN, Takahashi N, Sawada K, Fei Y, Soh S, Lee WH, Huang JW, Allen JC Jr, Woo XY, Nagarajan N, Kumar V, Thalamuthu A, Poh WT, Ang AL, Mya HT, How GF, Yang LY, Koh LP, Chowbay B, Chang CT, Nadarajan VS, Chng WJ, Than H, Lim LC, Goh YT, Zhang S, Poh D, Tan P, Seet JE, Ang MK, Chau NM, Ng QS, Tan DS, Soda M, Isobe K, Nöthen MM, Wong TY, Shahab A, Ruan X, Cacheux-Rataboul V, Sung WK, Tan EH, Yatabe Y, Mano H, Soo RA, Chin TM, Lim WT, Ruan Y, Ong ST. A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer. Nat Med 2012; 18:521-8.
    • ERBB2
    • R2 Yu HA, Arcila ME, Rekhtman N, Sima CS, Zakowski MF, Pao W, Kris MG, Miller VA, Ladanyi M, Riely GJ. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res 2013; 19:2240-7.
    • EGFR
    • R2 Yasuda H, Park E, Yun CH, Sng NJ, Lucena-Araujo AR, Yeo WL, Huberman MS, Cohen DW, Nakayama S, Ishioka K, Yamaguchi N, Hanna M, Oxnard GR, Lathan CS, Moran T, Sequist LV, Chaft JE, Riely GJ, Arcila ME, Soo RA, Meyerson M, Eck MJ, Kobayashi SS, Costa DB. Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer. Sci Transl Med 2013; 5:216ra177.
    • R2 Matsushima S, Ohtsuka K, Ohnishi H, Fujiwara M, Nakamura H, Morii T, Kishino T, Goto H, Watanabe T. V843I, a lung cancer predisposing EGFR mutation, is responsible for resistance to EGFR tyrosine kinase inhibitors. J Thorac Oncol 2014; 9:1377-84.
    • EGFR+RB1
    • R2 Niederst MJ, Sequist LV, Poirier JT, Mermel CH, Lockerman EL, Garcia AR, Katayama R, Costa C, Ross KN, Moran T, Howe E, Fulton LE, Mulvey HE, Bernardo LA, Mohamoud F, Miyoshi N, VanderLaan PA, Costa DB, Jänne PA, Borger DR, Ramaswamy S, Shioda T, Iafrate AJ, Getz G, Rudin CM, Mino-Kenudson M, Engelman JA. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat Commun 2015; 6:6377.
    • FBXW7
    • R2 Xiao Y, Yin C, Wang Y, Lv H, Wang W, Huang Y, Perez-Losada J, Snijders AM, Mao JH, Zhang P. FBXW7 deletion contributes to lung tumor development and confers resistance to gefitinib therapy. Mol Oncol 2018; 12:883-895.
    • EGFR+ROS1
    • R2 Zeng L, Yang N, Zhang Y. GOPC-ROS1 Rearrangement as an Acquired Resistance Mechanism to Osimertinib and Responding to Crizotinib Combined Treatments in Lung Adenocarcinoma. J Thorac Oncol 2018; 13:e114-e116.
    • EGFR+RET
    • R2 Piotrowska Z, Isozaki H, Lennerz JK, Gainor JF, Lennes IT, Zhu VW, Marcoux N, Banwait MK, Digumarthy SR, Su W, Yoda S, Riley AK, Nangia V, Lin JJ, Nagy RJ, Lanman RB, Dias-Santagata D, Mino-Kenudson M, Iafrate AJ, Heist RS, Shaw AT, Evans EK, Clifford C, Ou SI, Wolf B, Hata AN, Sequist LV. Landscape of Acquired Resistance to Osimertinib in EGFR-Mutant NSCLC and Clinical Validation of Combined EGFR and RET Inhibition with Osimertinib and BLU-667 for Acquired RET Fusion. Cancer Discov 2018; 8:1529-1539.
    • EGFR+RB1, EGFR+TP53
    • R2 Marcoux N, Gettinger SN, O'Kane G, Arbour KC, Neal JW, Husain H, Evans TL, Brahmer JR, Muzikansky A, Bonomi PD, Del Prete S, Wurtz A, Farago AF, Dias-Santagata D, Mino-Kenudson M, Reckamp KL, Yu HA, Wakelee HA, Shepherd FA, Piotrowska Z, Sequist LV. EGFR-Mutant Adenocarcinomas That Transform to Small-Cell Lung Cancer and Other Neuroendocrine Carcinomas: Clinical Outcomes. J Clin Oncol 2019; 37:278-285.
    • MET
    • R2 Lai GGY, Lim TH, Lim J, Liew PJR, Kwang XL, Nahar R, Aung ZW, Takano A, Lee YY, Lau DPX, Tan GS, Tan SH, Tan WL, Ang MK, Toh CK, Tan BS, Devanand A, Too CW, Gogna A, Ong BH, Koh TPT, Kanesvaran R, Ng QS, Jain A, Rajasekaran T, Yuan J, Lim TKH, Lim AST, Hillmer AM, Lim WT, Iyer NG, Tam WL, Zhai W, Tan EH, Tan DSW. Clonal MET Amplification as a Determinant of Tyrosine Kinase Inhibitor Resistance in Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer. J Clin Oncol 2019; 37:876-884.
    • EGFR+ALK, EGFR+RET
    • R2 Offin M, Somwar R, Rekhtman N, Benayed R, Chang JC, Plodkowski A, Lui AJW, Eng J, Rosenblum M, Li BT, Riely GJ, Rudin CM, Kris MG, Travis W, Drilon A, Arcila ME, Ladanyi M, Yu HA. Acquired ALK and RET Gene Fusions as Mechanisms of Resistance to Osimertinib in EGFR-Mutant Lung Cancers. JCO Precis Oncol 2018;2.
    • EGFR
    • R2 Liang SK, Ko JC, Yang JC, Shih JY. Afatinib is effective in the treatment of lung adenocarcinoma with uncommon EGFR p.L747P and p.L747S mutations. Lung Cancer 2019; 133:103-109.
    • R2 Byeon S, Hong JY, Lee J, Nam DH, Park SH, Park JO, Park YS, Lim HY, Kang WK, Kim ST. Use of Gefitinib in EGFR-Amplified Refractory Solid Tumors: An Open-Label, Single-Arm, Single-Center Prospective Pilot Study. Target Oncol 2020; 15:185-192.
    • R2 Xu H, Li W, Yang G, Li J, Yang L, Xu F, Yang Y, Ying J, Wang Y. Heterogeneous Response to First-Generation Tyrosine Kinase Inhibitors in Non-Small-Cell Lung Cancers with Different EGFR Exon 19 Mutations. Target Oncol 2020; 15:357-364.
    • R2 Wei Q, Zhang J, Chen D, Li S, Liu Y. Primary resistance to gefitinib in a patient with lung adenocarcinoma harboring an EGFR exon 19 L747-A750>P mutation. Lung Cancer 2020; 148:175-176.
    • R2 Lee C, Kim M, Kim DW, Kim TM, Kim S, Im SW, Jeon YK, Keam B, Ku JL, Heo DS. Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non-Small Cell Lung Cancer. Cancer Res Treat 2021 May 3. [Epub ahead of print]
    • R2 Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 2021; 597:732-737.
    • EGFR
    • 1 Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304:1497-500.
    • 1 Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361:947-57.
    • 1 Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010; 362:2380-8.
    • EGFR
    • 2 Gergis C, Rangachari D, Fujii M, Varkaris A, VanderLaan PA, Kobayashi S, Costa DB. EGFR-A763_Y764insFQEA: A unique exon 20 insertion mutation that displays sensitivity to all classes of approved lung cancer EGFR tyrosine kinase inhibitors. J Clin Oncol 2019; 37(15_suppl):
    • 2 Costa DB. Kinase inhibitor-responsive genotypes in EGFR mutated lung adenocarcinomas: moving past common point mutations or indels into uncommon kinase domain duplications and rearrangements. Transl Lung Cancer Res 2016; 5:331-7.
    • 2 Li K, Yang M, Liang N, Li S. Determining EGFR-TKI sensitivity of G719X and other uncommon EGFR mutations in non-small cell lung cancer: Perplexity and solution (Review). Oncol Rep 2017; 37:1347-1358.
    • EGFR
    • 3 Lin YT, Liu YN, Wu SG, Yang JC, Shih JY. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor-sensitive Exon 19 Insertion and Exon 20 Insertion in Patients With Advanced Non-Small-cell Lung Cancer. Clin Lung Cancer 2017; 18:324-332.e1.
    • 3 Zhu C, Zhuang W, Chen L, Yang W, Ou WB. Frontiers of ctDNA, targeted therapies, and immunotherapy in non-small-cell lung cancer. Transl Lung Cancer Res 2020; 9:111-138.
    • EGFR
    • 4 Ozer BH, Wiepz GJ, Bertics PJ. Activity and cellular localization of an oncogenic glioblastoma multiforme-associated EGF receptor mutant possessing a duplicated kinase domain. Oncogene 2010; 29:855-64.
    • 4 Yang TY, Tsai CR, Chen KC, Hsu KH, Lee HM, Chang GC. Good response to gefitinib in a lung adenocarcinoma harboring a heterozygous complex mutation of L833V and H835L in epidermal growth factor receptor gene. J Clin Oncol 2011; 29:e468-9.
    • 4 Ackerman A, Goldstein MA, Kobayashi S, Costa DB. EGFR delE709_T710insD: a rare but potentially EGFR inhibitor responsive mutation in non-small-cell lung cancer. J Thorac Oncol 2012; 7:e19-20.
    • 4 Wang F, Fu S, Shao Q, Zhou YB, Zhang X, Zhang X, Xue C, Lin JG, Huang LX, Zhang L, Zhang WM, Shao JY. High EGFR copy number predicts benefits from tyrosine kinase inhibitor treatment for non-small cell lung cancer patients with wild-type EGFR. J Transl Med 2013; 11:90.
    • 4 Kobayashi Y, Togashi Y, Yatabe Y, Mizuuchi H, Jangchul P, Kondo C, Shimoji M, Sato K, Suda K, Tomizawa K, Takemoto T, Hida T, Nishio K, Mitsudomi T. EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIs. Clin Cancer Res 2015; 21:5305-13.
    • 4 Gallant JN, Sheehan JH, Shaver TM, Bailey M, Lipson D, Chandramohan R, Red Brewer M, York SJ, Kris MG, Pietenpol JA, Ladanyi M, Miller VA, Ali SM, Meiler J, Lovly CM. EGFR Kinase Domain Duplication (EGFR-KDD) Is a Novel Oncogenic Driver in Lung Cancer That Is Clinically Responsive to Afatinib. Cancer Discov 2015; 5:1155-63.
    • 4 Baik CS, Wu D, Smith C, Martins RG, Pritchard CC. Durable Response to Tyrosine Kinase Inhibitor Therapy in a Lung Cancer Patient Harboring Epidermal Growth Factor Receptor Tandem Kinase Domain Duplication. J Thorac Oncol 2015; 10:e97-9.
    • 4 Kuiper JL, Hashemi SM, Thunnissen E, Snijders PJ, Grünberg K, Bloemena E, Sie D, Postmus PE, Heideman DA, Smit EF. Non-classic EGFR mutations in a cohort of Dutch EGFR-mutated NSCLC patients and outcomes following EGFR-TKI treatment. Br J Cancer 2016; 115:1504-1512.
    • 4 Wang J, Li X, Xue X, Ou Q, Wu X, Liang Y, Wang X, You M, Shao YW, Zhang Z, Zhang S. Clinical outcomes of EGFR kinase domain duplication to targeted therapies in NSCLC. Int J Cancer 2019; 144:2677-2682.
    • 4 Wang C, Xu F, Shen J, Zhang L, Zhang J, Jin J, Ampollini L, van Schil P, Kimura H, Grossi F, Suda K, Zhang B, Ma D; written on behalf of the AME Lung Cancer Collaborative Group. Successful treatment of lung adenocarcinoma with gefitinib based on EGFR gene amplification. J Thorac Dis 2018; 10:E779-E783.
    • 4 Peng X, Long X, Liu L, Zeng L, Yang H, Jiang W, Liao D, Li K, Wang J, Lizaso A, Mao X, Xu Q, Mansfield AS, Yang N, Zhang Y. Clinical impact of uncommon epidermal growth factor receptor exon 19 insertion-deletion variants on epidermal growth factor receptor-tyrosine kinase inhibitor efficacy in non-small-cell lung cancer. Eur J Cancer 2020; 141:199-208.
    • 4 Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 2021; 597:732-737.
    • 4 Maron SB, Moya S, Morano F, Emmett MJ, Chou JF, Sabwa S, Walch H, Peterson B, Schrock AB, Zhang L, Janjigian YY, Chalasani S, Ku GY, Disel U, Enzinger P, Uboha N, Kato S, Yoshino T, Shitara K, Nakamura Y, Saeed A, Kasi P, Chao J, Lee J, Capanu M, Wainberg Z, Petty R, Pietrantonio F, Klempner SJ, Catenacci DVT. Epidermal Growth Factor Receptor Inhibition in Epidermal Growth Factor Receptor-Amplified Gastroesophageal Cancer: Retrospective Global Experience. J Clin Oncol 2022 Mar 29:JCO2102453. [Epub ahead of print]
    • Gefitinib + Gemcitabine
    • EGFR+ERRFI1
    • 4 Cairns J, Fridley BL, Jenkins GD, Zhuang Y, Yu J, Wang L. Differential roles of ERRFI1 in EGFR and AKT pathway regulation affect cancer proliferation. EMBO Rep 2018; 19(3). pii: e44767.
    • Gefitinib + Savolitinib
    • EGFR+MET
    • 4 Wu YL, Zhang L, Kim DW, Liu X, Lee DH, Yang JC, Ahn MJ, Vansteenkiste JF, Su WC, Felip E, Chia V, Glaser S, Pultar P, Zhao S, Peng B, Akimov M, Tan DSW. Phase Ib/II Study of Capmatinib (INC280) Plus Gefitinib After Failure of Epidermal Growth Factor Receptor (EGFR) Inhibitor Therapy in Patients With EGFR-Mutated, MET Factor-Dysregulated Non-Small-Cell Lung Cancer. J Clin Oncol 2018; 36:3101-3109.
    • Gemtuzumab Ozogamicin
    • CD33
    • 1B Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol 2014; 32:3021-32.
    • Gilteritinib
    • FLT3
    • 1B Perl AE, Altman JK, Cortes J, Smith C, Litzow M, Baer MR, Claxton D, Erba HP, Gill S, Goldberg S, Jurcic JG, Larson RA, Liu C, Ritchie E, Schiller G, Spira AI, Strickland SA, Tibes R, Ustun C, Wang ES, Stuart R, Röllig C, Neubauer A, Martinelli G, Bahceci E, Levis M. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study. Lancet Oncol 2017; 18:1061-1075.
    • 1B Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, Montesinos P, Baer MR, Larson RA, Ustun C, Fabbiano F, Erba HP, Di Stasi A, Stuart R, Olin R, Kasner M, Ciceri F, Chou WC, Podoltsev N, Recher C, Yokoyama H, Hosono N, Yoon SS, Lee JH, Pardee T, Fathi AT, Liu C, Hasabou N, Liu X, Bahceci E, Levis MJ. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N Engl J Med 2019; 381:1728-1740.
    • NRAS
    • R2 McMahon CM, Ferng T, Canaani J, Wang ES, Morrissette JJD, Eastburn DJ, Pellegrino M, Durruthy-Durruthy R, Watt CD, Asthana S, Lasater EA, DeFilippis R, Peretz CAC, McGary LHF, Deihimi S, Logan AC, Luger SM, Shah NP, Carroll M, Smith CC, Perl AE. Clonal Selection with RAS Pathway Activation Mediates Secondary Clinical Resistance to Selective FLT3 Inhibition in Acute Myeloid Leukemia. Cancer Discov 2019; 9:1050-1063.
    • Giredestrant
    • ESR1
    • 4 Jhaveri KL, Boni V, Sohn J, Villanueva-Vásquez R, Bardia A, Schmid P, Lim E, Patel JM, Perez-Fidalgo JA, Loi S, Im S, Kshirsagar S, Gates MR, Bond J, Eng-Wong J, Chang C, Turner NC, Miranda EL, García-Estévez L, Bellet M, Francisco , Hospital CRM, London , Cajal UKHURy, Madrid , Madrid SMACC, Madrid , Oncology SVdUHaVdIo, Barcelona , Spain . Safety and activity of single-agent giredestrant (GDC-9545) from a phase Ia/b study in patients (pts) with estrogen receptor-positive (ER+), HER2-negative locally advanced/metastatic breast cancer (LA/mBC). J Clin Oncol 2021; 39(15_suppl): 1017-1017.
    • Glesatinib
    • MET
    • R2 Recondo G, Bahcall M, Spurr LF, Che J, Ricciuti B, Leonardi GC, Lo YC, Li YY, Lamberti G, Nguyen T, Milan MSD, Venkatraman D, Umeton R, Paweletz CP, Albayrak A, Cherniack AD, Price KS, Fairclough SR, Nishino M, Sholl LM, Oxnard GR, Jänne PA, Awad MM. Molecular Mechanisms of Acquired Resistance to MET Tyrosine Kinase Inhibitors in Patients with MET Exon 14-Mutant NSCLC. Clin Cancer Res 2020; 26:2615-2625.
    • GnRH agonist
    • ESR1
    • R2 Jeselsohn R, Buchwalter G, De Angelis C, Brown M, Schiff R. ESR1 mutations—a mechanism for acquired endocrine resistance in breast cancer. Nat Rev Clin Oncol 2015; 12:573-83.
    • AR, AURKA, MYCN, RB1, TP53
    • R2 Watson PA, Arora VK, Sawyers CL. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nat Rev Cancer 2015; 15:701-11.
    • AR
    • 4 Munoz J, Wheler JJ, Kurzrock R. Androgen receptors beyond prostate cancer: an old marker as a new target. Oncotarget 2015; 6:592-603.
    • Goserelin
    • PGR
    • 1 McGuire WL, Horwitz KB, Pearson OH, Segaloff A. Current status of estrogen and progesterone receptors in breast cancer. Cancer 1977; 39(6 Suppl):2934-47.
    • 1 Kiang DT, Kennedy BJ. Tamoxifen (antiestrogen) therapy in advanced breast cancer. Ann Intern Med 1977; 87:687-90.
    • 1 A randomized crossover trial in postmenopausal patients with advanced breast cancer. Oral high-dose medroxyprogesterone acetate versus tamoxifen.. Cancer 1986; 58:7-13.
    • 1 Muss HB, Wells HB, Paschold EH, Black WR, Cooper MR, Capizzi RL, Christian R, Cruz JM, Jackson DV, Powell BL, et al. Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association. J Clin Oncol 1988; 6:1098-106.
    • 1 Stuart NS, Warwick J, Blackledge GR, Spooner D, Keen C, Taylor AR, Tyrell C, Webster DJ, Earl H. A randomised phase III cross-over study of tamoxifen versus megestrol acetate in advanced and recurrent breast cancer. Eur J Cancer 1996; 32A:1888-92.
    • ESR1, PGR
    • 1 Taylor CW, Green S, Dalton WS, Martino S, Rector D, Ingle JN, Robert NJ, Budd GT, Paradelo JC, Natale RB, Bearden JD, Mailliard JA, Osborne CK. Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer: an intergroup study. J Clin Oncol 1998; 16:994-9.
    • PGR
    • 1 The Exemestane Study Group. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial.. J Clin Oncol 2000; 18:1399-411.
    • 1 Mouridsen H, Gershanovich M, Sun Y, Pérez-Carrión R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Jänicke F, Pluzanska A, Dank M, Becquart D, Bapsy PP, Salminen E, Snyder R, Lassus M, Verbeek JA, Staffler B, Chaudri-Ross HA, Dugan M. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 2001; 19:2596-606.
    • 1 Bonneterre J, Buzdar A, Nabholtz JM, Robertson JF, Thürlimann B, von Euler M, Sahmoud T, Webster A, Steinberg M; Arimidex Writing Committee; Investigators Committee Members. Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma. Cancer 2001; 92:2247-58.
    • Gunagratinib
    • FGFR2
    • 4 Guo Y, Yuan C, Ying J, Zhu X, Luan G, Zhang B, Zhao R, Li J. Phase I result of ICP-192 (gunagratinib), a highly selective irreversible FGFR inhibitor, in patients with advanced solid tumors harboring FGFR pathway alterations. J Clin Oncol 2021; 39(15_suppl): 4092-4092.
    • H
    • H3B-6545
    • ESR1
    • R2 Hamilton EP, Wang JS, Pluard TJ, Johnston SRD, Morikawa A, Dees EC, Jones RH, Haley BB, Armstrong AC, Cohen AL, Munster PN, Wright GLS, Kayali F, Korpal M, Xiao JA, Long J, Destenaves B, Gao L, Gualberto A, Juric D. Phase I/II study of H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. J Clin Oncol 2021; 39(15_suppl): 1018-1018.
    • ESR1
    • 4 Hamilton EP, Wang JS, Pluard TJ, Johnston SRD, Morikawa A, Dees EC, Jones RH, Haley BB, Armstrong AC, Cohen AL, Munster PN, Wright GLS, Kayali F, Korpal M, Xiao JA, Long J, Destenaves B, Gao L, Gualberto A, Juric D. Phase I/II study of H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. J Clin Oncol 2021; 39(15_suppl): 1018-1018.
    • H3B-8800
    • SF3B1, SRSF2
    • 4 Seiler M, Yoshimi A, Darman R, Chan B, Keaney G, Thomas M, Agrawal AA, Caleb B, Csibi A, Sean E, Fekkes P, Karr C, Klimek V, Lai G, Lee L, Kumar P, Lee SC, Liu X, Mackenzie C, Meeske C, Mizui Y, Padron E, Park E, Pazolli E, Peng S, Prajapati S, Taylor J, Teng T, Wang J, Warmuth M, Yao H, Yu L, Zhu P, Abdel-Wahab O, Smith PG, Buonamici S. H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers. Nat Med 2018; 24:497-504.
    • SF3B1
    • 4 Steensma DP, Wermke M, Klimek VM, Greenberg PL, Font P, Komrokji RS, Yang J, Brunner AM, Carraway HE, Ades L, Al-Kali A, Alonso-Dominguez JM, Alfonso-Piérola A, Coombs CC, Deeg HJ, Flinn I, Foran JM, Garcia-Manero G, Maris MB, McMasters M, Micol JB, De Oteyza JP, Thol F, Wang ES, Watts JM, Taylor J, Stone R, Gourineni V, Marino AJ, Yao H, Destenaves B, Yuan X, Yu K, Dar S, Ohanjanian L, Kuida K, Xiao J, Scholz C, Gualberto A, Platzbecker U. Phase I First-in-Human Dose Escalation Study of the oral SF3B1 modulator H3B-8800 in myeloid neoplasms. Leukemia 2021; 35:3542-3550.
    • H3Mab-17
    • ERBB3
    • 4 Asano T, Ohishi T, Takei J, Nakamura T, Nanamiya R, Hosono H, Tanaka T, Sano M, Harada H, Kawada M, Kaneko MK, Kato Y. Anti‑HER3 monoclonal antibody exerts antitumor activity in a mouse model of colorectal adenocarcinoma. Oncol Rep 2021; 46(2). pii: 173.
    • HB-201
    • HPV genotype
    • 4 Ho AL, Posner MR, Niu J, Fu S, Leidner RS, Pearson AT, Chung KY, Richardson DL, Wang D, Pimentel A, Nieva JJ, Rosenberg A, Burman B, Iacobucci C, Qing X, Hwang A, Katchar K, Schlienger K, Matushansky I, Pfister DG. First report of the safety/tolerability and preliminary antitumor activity of HB-201 and HB-202, an arenavirus-based cancer immunotherapy, in patients with HPV16+ cancers. J Clin Oncol 2021; 39(15_suppl): 2502-2502.
    • HB-201 + HB-202
    • HPV genotype
    • 4 Ho AL, Posner MR, Niu J, Fu S, Leidner RS, Pearson AT, Chung KY, Richardson DL, Wang D, Pimentel A, Nieva JJ, Rosenberg A, Burman B, Iacobucci C, Qing X, Hwang A, Katchar K, Schlienger K, Matushansky I, Pfister DG. First report of the safety/tolerability and preliminary antitumor activity of HB-201 and HB-202, an arenavirus-based cancer immunotherapy, in patients with HPV16+ cancers. J Clin Oncol 2021; 39(15_suppl): 2502-2502.
    • Halofuginone
    • MYCN
    • 4 Niemas-Teshiba R, Matsuno R, Wang LL, Tang XX, Chiu B, Zeki J, Coburn J, Ornell K, Naranjo A, Van Ryn C, London WB, Hogarty MD, Gastier-Foster JM, Look AT, Park JR, Maris JM, Cohn SL, Seeger RC, Asgharzadeh S, Ikegaki N, Shimada H. MYC-family protein overexpression and prominent nucleolar formation represent prognostic indicators and potential therapeutic targets for aggressive high-MKI neuroblastomas: a report from the children's oncology group. Oncotarget 2017; 9:6416-6432. eCollection 2018 Jan 19.
    • I
    • ICP-723
    • NTRK1, NTRK2, NTRK3
    • 4 . . [DOI:]
    • IDE196
    • GNA11, GNAQ, PRKCA, PRKCB
    • 4 Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions [NCT03947385]
    • II-B08
    • NRAS
    • R2 Valencia-Sama I, Ladumor Y, Kee L, Adderley T, Christopher G, Robinson CM, Kano Y, Ohh M, Irwin MS. NRAS Status Determines Sensitivity to SHP2 Inhibitor Combination Therapies Targeting the RAS-MAPK Pathway in Neuroblastoma. Cancer Res 2020; 80:3413-3423.
    • IK-930
    • NF2, TAZ, YAP1
    • 4 Oral TEAD Inhibitor Targeting the Hippo Pathway in Subjects With Advanced Solid Tumors [NCT05228015]
    • Ibrutinib
    • CD20
    • 1 Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, Barrientos JC, Chmielowska E, Radford J, Stilgenbauer S, Dreyling M, Jedrzejczak WW, Johnson P, Spurgeon SE, Li L, Zhang L, Newberry K, Ou Z, Cheng N, Fang B, McGreivy J, Clow F, Buggy JJ, Chang BY, Beaupre DM, Kunkel LA, Blum KA. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med 2013; 369:507-16.
    • CD20
    • 1B Dimopoulos MA, Tedeschi A, Trotman J, García-Sanz R, Macdonald D, Leblond V, Mahe B, Herbaux C, Tam C, Orsucci L, Palomba ML, Matous JV, Shustik C, Kastritis E, Treon SP, Li J, Salman Z, Graef T, Buske C; iNNOVATE Study Group and the European Consortium for Waldenström’s Macroglobulinemia. Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström's Macroglobulinemia. N Engl J Med 2018; 378:2399-2410.
    • MYD88
    • 2 Treon SP, Tripsas CK, Meid K, Warren D, Varma G, Green R, Argyropoulos KV, Yang G, Cao Y, Xu L, Patterson CJ, Rodig S, Zehnder JL, Aster JC, Harris NL, Kanan S, Ghobrial I, Castillo JJ, Laubach JP, Hunter ZR, Salman Z, Li J, Cheng M, Clow F, Graef T, Palomba ML, Advani RH. Ibrutinib in previously treated Waldenström's macroglobulinemia. N Engl J Med 2015; 372:1430-40.
    • MYD88
    • 3 Treon SP, Xu L, Hunter Z. MYD88 Mutations and Response to Ibrutinib in Waldenström's Macroglobulinemia. N Engl J Med 2015; 373:584-6.
    • TP53
    • 3 Ahn IE, Tian X, Wiestner A. Ibrutinib for Chronic Lymphocytic Leukemia with TP53 Alterations. N Engl J Med 2020; 383:498-500.
    • Ibrutinib + Rituximab
    • CD20
    • 1B Dimopoulos MA, Tedeschi A, Trotman J, García-Sanz R, Macdonald D, Leblond V, Mahe B, Herbaux C, Tam C, Orsucci L, Palomba ML, Matous JV, Shustik C, Kastritis E, Treon SP, Li J, Salman Z, Graef T, Buske C; iNNOVATE Study Group and the European Consortium for Waldenström’s Macroglobulinemia. Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström's Macroglobulinemia. N Engl J Med 2018; 378:2399-2410.
    • 1B Shanafelt TD, Wang XV, Kay NE, Hanson CA, O'Brien S, Barrientos J, Jelinek DF, Braggio E, Leis JF, Zhang CC, Coutre SE, Barr PM, Cashen AF, Mato AR, Singh AK, Mullane MP, Little RF, Erba H, Stone RM, Litzow M, Tallman M. Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia. N Engl J Med 2019; 381:432-443.
    • Icotinib
    • EGFR
    • 4 Li J, Yan J, Cao R, Du G, Zhao G. Lung Adenocarcinoma Harboring EGFR Kinase Domain Duplication (EGFR-KDD) Confers Sensitivity to Osimertinib and Nivolumab: A Case Report. Front Oncol 2020; 10:575739. eCollection 2020.
    • Imatinib
    • KIT
    • 1 Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002; 347:472-80.
    • ABL1
    • 1 O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, Cornelissen JJ, Fischer T, Hochhaus A, Hughes T, Lechner K, Nielsen JL, Rousselot P, Reiffers J, Saglio G, Shepherd J, Simonsson B, Gratwohl A, Goldman JM, Kantarjian H, Taylor K, Verhoef G, Bolton AE, Capdeville R, Druker BJ; IRIS Investigators. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003; 348:994-1004.
    • KIT
    • 1 Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006; 368:1329-38.
    • PDGFRA
    • 1 Metzgeroth G, Walz C, Erben P, Popp H, Schmitt-Graeff A, Haferlach C, Fabarius A, Schnittger S, Grimwade D, Cross NC, Hehlmann R, Hochhaus A, Reiter A. Safety and efficacy of imatinib in chronic eosinophilic leukaemia and hypereosinophilic syndrome: a phase-II study. Br J Haematol 2008; 143:707-15.
    • PDGFB
    • 1 Labropoulos SV, Razis ED. Imatinib in the treatment of dermatofibrosarcoma protuberans. Biologics. 2007 Dec;1(4):347-53.
    • PDGFRA
    • 1B Gleich GJ, Leiferman KM, Pardanani A, Tefferi A, Butterfield JH. Treatment of hypereosinophilic syndrome with imatinib mesilate. Lancet 2002; 359:1577-8.
    • 1B Results of a multicenter prospective study. The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome.. Haematologica 2007; 92:1173-9.
    • PDGFRB
    • 1B Cheah CY, Burbury K, Apperley JF, Huguet F, Pitini V, Gardembas M, Ross DM, Forrest D, Genet P, Rousselot P, Patton N, Smith G, Dunbar CE, Ito S, Aguiar RC, Odenike O, Gimelfarb A, Cross NC, Seymour JF. Patients with myeloid malignancies bearing PDGFRB fusion genes achieve durable long-term remissions with imatinib. Blood 2014; 123:3574-7.
    • PDGFRA
    • R1 Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, McGreevey LS, Chen CJ, Van den Abbeele AD, Druker BJ, Kiese B, Eisenberg B, Roberts PJ, Singer S, Fletcher CD, Silberman S, Dimitrijevic S, Fletcher JA. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 2003; 21:4342-9.
    • ABL1
    • R1 Nardi V, Azam M, Daley GQ. Mechanisms and implications of imatinib resistance mutations in BCR-ABL. Curr Opin Hematol 2004; 11:35-43.
    • R1 Redaelli S, Piazza R, Rostagno R, Magistroni V, Perini P, Marega M, Gambacorti-Passerini C, Boschelli F. Activity of bosutinib, dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants. J Clin Oncol 2009; 27:469-71.
    • R1 Khoury HJ, Cortes JE, Kantarjian HM, Gambacorti-Passerini C, Baccarani M, Kim DW, Zaritskey A, Countouriotis A, Besson N, Leip E, Kelly V, Brümmendorf TH. Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. Blood 2012; 119:3403-12.
    • PDGFRA
    • R1 Heinrich MC, Marino-Enriquez A, Presnell A, Donsky RS, Griffith DJ, McKinley A, Patterson J, Taguchi T, Liang CW, Fletcher JA. Sorafenib inhibits many kinase mutations associated with drug-resistant gastrointestinal stromal tumors. Mol Cancer Ther 2012; 11:1770-80.
    • PDGFRA
    • R2 Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, Kutok J, Clark J, Galinsky I, Griffin JD, Cross NC, Tefferi A, Malone J, Alam R, Schrier SL, Schmid J, Rose M, Vandenberghe P, Verhoef G, Boogaerts M, Wlodarska I, Kantarjian H, Marynen P, Coutre SE, Stone R, Gilliland DG. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 2003; 348:1201-14.
    • KIT
    • R2 Akin C, Brockow K, D'Ambrosio C, Kirshenbaum AS, Ma Y, Longley BJ, Metcalfe DD. Effects of tyrosine kinase inhibitor STI571 on human mast cells bearing wild-type or mutated c-kit. Exp Hematol 2003; 31:686-92.
    • R2 Hotte SJ, Winquist EW, Lamont E, MacKenzie M, Vokes E, Chen EX, Brown S, Pond GR, Murgo A, Siu LL. Imatinib mesylate in patients with adenoid cystic cancers of the salivary glands expressing c-kit: a Princess Margaret Hospital phase II consortium study. J Clin Oncol 2005; 23:585-90.
    • R2 Pfeffer MR, Talmi Y, Catane R, Symon Z, Yosepovitch A, Levitt M. A phase II study of Imatinib for advanced adenoid cystic carcinoma of head and neck salivary glands. Oral Oncol 2007; 43:33-6.
    • NF1+KIT
    • R2 Mussi C, Schildhaus HU, Gronchi A, Wardelmann E, Hohenberger P. Therapeutic consequences from molecular biology for gastrointestinal stromal tumor patients affected by neurofibromatosis type 1. Clin Cancer Res 2008; 14:4550-5.
    • KIT
    • R2 Gajiwala KS, Wu JC, Christensen J, Deshmukh GD, Diehl W, DiNitto JP, English JM, Greig MJ, He YA, Jacques SL, Lunney EA, McTigue M, Molina D, Quenzer T, Wells PA, Yu X, Zhang Y, Zou A, Emmett MR, Marshall AG, Zhang HM, Demetri GD. KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. Proc Natl Acad Sci U S A 2009; 106:1542-7.
    • PDGFRA
    • R2 Metzgeroth G, Erben P, Martin H, Mousset S, Teichmann M, Walz C, Klippstein T, Hochhaus A, Cross NC, Hofmann WK, Reiter A. Limited clinical activity of nilotinib and sorafenib in FIP1L1-PDGFRA positive chronic eosinophilic leukemia with imatinib-resistant T674I mutation. Leukemia 2012; 26:162-4.
    • R2 Heinrich MC, Marino-Enriquez A, Presnell A, Donsky RS, Griffith DJ, McKinley A, Patterson J, Taguchi T, Liang CW, Fletcher JA. Sorafenib inhibits many kinase mutations associated with drug-resistant gastrointestinal stromal tumors. Mol Cancer Ther 2012; 11:1770-80.
    • KIT
    • R2 Todd JR, Becker TM, Kefford RF, Rizos H. Secondary c-Kit mutations confer acquired resistance to RTK inhibitors in c-Kit mutant melanoma cells. Pigment Cell Melanoma Res 2013; 26:518-26.
    • KIT, NRAS
    • R2 Hodi FS, Corless CL, Giobbie-Hurder A, Fletcher JA, Zhu M, Marino-Enriquez A, Friedlander P, Gonzalez R, Weber JS, Gajewski TF, O'Day SJ, Kim KB, Lawrence D, Flaherty KT, Luke JJ, Collichio FA, Ernstoff MS, Heinrich MC, Beadling C, Zukotynski KA, Yap JT, Van den Abbeele AD, Demetri GD, Fisher DE. Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. J Clin Oncol 2013; 31:3182-90.
    • PDGFRA
    • R2 Van Dievel J, Sciot R, Delcroix M, Vandeweyer RO, Debiec-Rychter M, Dewaele B, Cornillie J, Van Cann T, Meyns B, Schöffski P. Single-Center Experience with Intimal Sarcoma, an Ultra-Orphan, Commonly Fatal Mesenchymal Malignancy. Oncol Res Treat 2017;40:353-359.
    • KIT
    • R2 Hemming ML, Heinrich MC, Bauer S, George S. Translational insights into gastrointestinal stromal tumor and current clinical advances. Ann Oncol 2018; 29:2037-2045.
    • LZTR1, NF1, PTPN11, WT1
    • R2 Bigenzahn JW, Collu GM, Kartnig F, Pieraks M, Vladimer GI, Heinz LX, Sedlyarov V, Schischlik F, Fauster A, Rebsamen M, Parapatics K, Blomen VA, Müller AC, Winter GE, Kralovics R, Brummelkamp TR, Mlodzik M, Superti-Furga G. LZTR1 is a regulator of RAS ubiquitination and signaling. Science 2018; 362:1171-1177.
    • KIT
    • R2 Serrano C, Mariño-Enríquez A, Tao DL, Ketzer J, Eilers G, Zhu M, Yu C, Mannan AM, Rubin BP, Demetri GD, Raut CP, Presnell A, McKinley A, Heinrich MC, Czaplinski JT, Sicinska E, Bauer S, George S, Fletcher JA. Complementary activity of tyrosine kinase inhibitors against secondary kit mutations in imatinib-resistant gastrointestinal stromal tumours. Br J Cancer 2019; 120:612-620.
    • R2 Smith BD, Kaufman MD, Lu WP, Gupta A, Leary CB, Wise SC, Rutkoski TJ, Ahn YM, Al-Ani G, Bulfer SL, Caldwell TM, Chun L, Ensinger CL, Hood MM, McKinley A, Patt WC, Ruiz-Soto R, Su Y, Telikepalli H, Town A, Turner BA, Vogeti L, Vogeti S, Yates K, Janku F, Abdul Razak AR, Rosen O, Heinrich MC, Flynn DL. Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants. Cancer Cell 2019; 35:738-751.e9.
    • R2 Serrano C, Mariño-Enríquez A, Tao DL, Ketzer J, Eilers G, Zhu M, Yu C, Mannan AM, Rubin BP, Demetri GD, Raut CP, Presnell A, McKinley A, Heinrich MC, Czaplinski JT, Sicinska E, Bauer S, George S, Fletcher JA. Correction: Complementary activity of tyrosine kinase inhibitors against secondary kit mutations in imatinib-resistant gastrointestinal stromal tumours. Br J Cancer 2019; 121:281.
    • R2 Apsel Winger B, Cortopassi WA, Garrido Ruiz D, Ding L, Jang K, Leyte-Vidal A, Zhang N, Esteve-Puig R, Jacobson MP, Shah NP. ATP-Competitive Inhibitors Midostaurin and Avapritinib Have Distinct Resistance Profiles in Exon 17-Mutant KIT. Cancer Res 2019; 79:4283-4292.
    • ABL1
    • 2 Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM, Capdeville R, Talpaz M. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001; 344:1038-42.
    • 2 O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, Cornelissen JJ, Fischer T, Hochhaus A, Hughes T, Lechner K, Nielsen JL, Rousselot P, Reiffers J, Saglio G, Shepherd J, Simonsson B, Gratwohl A, Goldman JM, Kantarjian H, Taylor K, Verhoef G, Bolton AE, Capdeville R, Druker BJ; IRIS Investigators. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003; 348:994-1004.
    • KIT
    • 2 Heinrich MC, Maki RG, Corless CL, Antonescu CR, Harlow A, Griffith D, Town A, McKinley A, Ou WB, Fletcher JA, Fletcher CD, Huang X, Cohen DP, Baum CM, Demetri GD. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol 2008; 26:5352-9.
    • ABL1
    • 3 Graux C, Cools J, Melotte C, Quentmeier H, Ferrando A, Levine R, Vermeesch JR, Stul M, Dutta B, Boeckx N, Bosly A, Heimann P, Uyttebroeck A, Mentens N, Somers R, MacLeod RA, Drexler HG, Look AT, Gilliland DG, Michaux L, Vandenberghe P, Wlodarska I, Marynen P, Hagemeijer A. Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia. Nat Genet 2004; 36:1084-9.
    • KIT
    • 3 Curtin JA, Busam K, Pinkel D, Bastian BC. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol 2006; 24:4340-6.
    • 3 Carvajal RD, Antonescu CR, Wolchok JD, Chapman PB, Roman RA, Teitcher J, Panageas KS, Busam KJ, Chmielowski B, Lutzky J, Pavlick AC, Fusco A, Cane L, Takebe N, Vemula S, Bouvier N, Bastian BC, Schwartz GK. KIT as a therapeutic target in metastatic melanoma. JAMA 2011; 305:2327-34.
    • 3 Chaix A, Arcangeli ML, Lopez S, Voisset E, Yang Y, Vita M, Letard S, Audebert S, Finetti P, Birnbaum D, Bertucci F, Aurrand-Lions M, Dubreuil P, De Sepulveda P. KIT-D816V oncogenic activity is controlled by the juxtamembrane docking site Y568-Y570. Oncogene 2014; 33:872-81.
    • 3 Hodi FS, Corless CL, Giobbie-Hurder A, Fletcher JA, Zhu M, Marino-Enriquez A, Friedlander P, Gonzalez R, Weber JS, Gajewski TF, O'Day SJ, Kim KB, Lawrence D, Flaherty KT, Luke JJ, Collichio FA, Ernstoff MS, Heinrich MC, Beadling C, Zukotynski KA, Yap JT, Van den Abbeele AD, Demetri GD, Fisher DE. Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. J Clin Oncol 2013; 31:3182-90.
    • 3 Hirai F, Edagawa M, Shimamatsu S, Toyozawa R, Toyokawa G, Nosaki K, Yamaguchi M, Seto T, Twakenoyama M, Ichinose Y. c-kit mutation-positive advanced thymic carcinoma successfully treated as a mediastinal gastrointestinal stromal tumor: A case report. Mol Clin Oncol 2016; 4:527-529.
    • 3 Remon J, Girard N, Mazieres J, Dansin E, Pichon E, Greillier L, Dubos C, Lindsay CR, Besse B. Sunitinib in patients with advanced thymic malignancies: Cohort from the French RYTHMIC network. Lung Cancer 2016; 97:99-104.
    • KIT
    • 4 Alcedo JC, Fábrega JM, Arosemena JR, Urrutia A. Imatinib mesylate as treatment for adenoid cystic carcinoma of the salivary glands: report of two successfully treated cases. Head Neck 2004; 26:829-31.
    • PDGFRA
    • 4 Corless CL, Schroeder A, Griffith D, Town A, McGreevey L, Harrell P, Shiraga S, Bainbridge T, Morich J, Heinrich MC. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol 2005; 23:5357-64.
    • KIT
    • 4 Faivre S, Raymond E, Casiraghi O, Temam S, Berthaud P. Imatinib mesylate can induce objective response in progressing, highly expressing KIT adenoid cystic carcinoma of the salivary glands. J Clin Oncol 2005; 23:6271-3; author reply 6273-4.
    • CSF1
    • 4 Blay JY, El Sayadi H, Thiesse P, Garret J, Ray-Coquard I. Complete response to imatinib in relapsing pigmented villonodular synovitis/tenosynovial giant cell tumor (PVNS/TGCT). Ann Oncol 2008; 19:821-2.
    • KIT
    • 4 Hamada S, Masago K, Mio T, Hirota S, Mishima M. Good clinical response to imatinib mesylate in atypical thymic carcinoid With KIT overexpression. J Clin Oncol 2011; 29:e9-10.
    • CSF1
    • 4 Cassier PA, Gelderblom H, Stacchiotti S, Thomas D, Maki RG, Kroep JR, van der Graaf WT, Italiano A, Seddon B, Dômont J, Bompas E, Wagner AJ, Blay JY. Efficacy of imatinib mesylate for the treatment of locally advanced and/or metastatic tenosynovial giant cell tumor/pigmented villonodular synovitis. Cancer 2012; 118:1649-55.
    • KIT
    • 4 Buti S, Donini M, Sergio P, Garagnani L, Schirosi L, Passalacqua R, Rossi G. Impressive response with imatinib in a heavily pretreated patient with metastatic c-KIT mutated thymic carcinoma. J Clin Oncol 2011; 29:e803-5.
    • PDGFRA
    • 4 Heinrich MC, Marino-Enriquez A, Presnell A, Donsky RS, Griffith DJ, McKinley A, Patterson J, Taguchi T, Liang CW, Fletcher JA. Sorafenib inhibits many kinase mutations associated with drug-resistant gastrointestinal stromal tumors. Mol Cancer Ther 2012; 11:1770-80.
    • ABL1
    • 4 Pang Y, Yu G, Butler M, Sindiri S, Song YK, Wei JS, Wen X, Chou HC, Quezado M, Pack S, Xi L, Abdullaev Z, Kim O, Ranjan A, Merchant M, Antony R, Boris L, Aboud O, Kamson D, Kaplan R, Mackey M, Camphausen K, Zaghloul K, Armstrong TS, Gilbert MR, Aldape K, Holdhoff M, Khan J, Wu J. Report of Canonical BCR-ABL1 Fusion in Glioblastoma. JCO Precis Oncol 2021; 5. pii: PO.20.00519. eCollection 2021.
    • Imatinib + Binimetinib
    • KIT
    • R2 Chi P, Qin LX, Nguyen B, Kelly CM, D'Angelo SP, Dickson MA, Gounder MM, Keohan ML, Movva S, Nacev BA, Rosenbaum E, Thornton KA, Crago AM, Yoon S, Ulaner G, Yeh R, Martindale M, Phelan HT, Biniakewitz MD, Warda S, Lee CJ, Berger MF, Schultz ND, Singer S, Hwang S, Chen Y, Antonescu CR, Tap WD. Phase II Trial of Imatinib Plus Binimetinib in Patients With Treatment-Naive Advanced Gastrointestinal Stromal Tumor. J Clin Oncol 2022; 40:997-1008.
    • KIT
    • 3 Chi P, Qin LX, Nguyen B, Kelly CM, D'Angelo SP, Dickson MA, Gounder MM, Keohan ML, Movva S, Nacev BA, Rosenbaum E, Thornton KA, Crago AM, Yoon S, Ulaner G, Yeh R, Martindale M, Phelan HT, Biniakewitz MD, Warda S, Lee CJ, Berger MF, Schultz ND, Singer S, Hwang S, Chen Y, Antonescu CR, Tap WD. Phase II Trial of Imatinib Plus Binimetinib in Patients With Treatment-Naive Advanced Gastrointestinal Stromal Tumor. J Clin Oncol 2022; 40:997-1008.
    • Imatinib + Hydroxyurea
    • KIT
    • 4 Reardon DA, Dresemann G, Taillibert S, Campone M, van den Bent M, Clement P, Blomquist E, Gordower L, Schultz H, Raizer J, Hau P, Easaw J, Gil M, Tonn J, Gijtenbeek A, Schlegel U, Bergstrom P, Green S, Weir A, Nikolova Z. Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma. Br J Cancer 2009; 101:1995-2004.
    • Imlunestrant
    • ESR1
    • 4 Jhaveri KL, Jeselsohn R, Lim E, Hamilton EP, Yonemori K, Beck JT, Kaufman PA, Sammons S, Bhave MA, Saura C, Calvo E, Meniawy T, Larson T, Ma CX, García-Corbacho J, Cao S, Estrem ST, Milata JL, Nguyen B, Beeram M, Louis , Barcelona/IDIBAPS MHCiPd, Barcelona , Company SELa, Indianapolis , Care ISCfC, Antonio S, TX . A phase 1a/b trial of imlunestrant (LY3484356), an oral selective estrogen receptor degrader (SERD) in ER-positive (ER+) advanced breast cancer (aBC) and endometrial endometrioid cancer (EEC): Monotherapy results from EMBER. J Clin Oncol 2022; 40(16_suppl): 1021-1021.
    • Inavolisib
    • PIK3CA
    • 4 Vasan N, Razavi P, Johnson JL, Shao H, Shah H, Antoine A, Ladewig E, Gorelick A, Lin TY, Toska E, Xu G, Kazmi A, Chang MT, Taylor BS, Dickler MN, Jhaveri K, Chandarlapaty S, Rabadan R, Reznik E, Smith ML, Sebra R, Schimmoller F, Wilson TR, Friedman LS, Cantley LC, Scaltriti M, Baselga J. Double PIK3CA mutations in cis increase oncogenicity and sensitivity to PI3Kα inhibitors. Science 2019; 366:714-723.
    • Infigratinib
    • FGFR3
    • R2 Chell V, Balmanno K, Little AS, Wilson M, Andrews S, Blockley L, Hampson M, Gavine PR, Cook SJ. Tumour cell responses to new fibroblast growth factor receptor tyrosine kinase inhibitors and identification of a gatekeeper mutation in FGFR3 as a mechanism of acquired resistance. Oncogene 2013; 32:3059-70.
    • FGFR2
    • R2 Byron SA, Chen H, Wortmann A, Loch D, Gartside MG, Dehkhoda F, Blais SP, Neubert TA, Mohammadi M, Pollock PM. The N550K/H mutations in FGFR2 confer differential resistance to PD173074, dovitinib, and ponatinib ATP-competitive inhibitors. Neoplasia 2013; 15:975-88.
    • R2 Helsten T, Schwaederle M, Kurzrock R. Fibroblast growth factor receptor signaling in hereditary and neoplastic disease: biologic and clinical implications. Cancer Metastasis Rev 2015; 34:479-96.
    • MET
    • R2 Kim SM, Kim H, Yun MR, Kang HN, Pyo KH, Park HJ, Lee JM, Choi HM, Ellinghaus P, Ocker M, Paik S, Kim HR, Cho BC. Activation of the Met kinase confers acquired drug resistance in FGFR-targeted lung cancer therapy. Oncogenesis 2016; 5:e241.
    • FGFR1
    • R2 Yoza K, Himeno R, Amano S, Kobashigawa Y, Amemiya S, Fukuda N, Kumeta H, Morioka H, Inagaki F. Biophysical characterization of drug-resistant mutants of fibroblast growth factor receptor 1. Genes Cells 2016; 21:1049-1058.
    • MET
    • R2 Malchers F, Ercanoglu M, Schütte D, Castiglione R, Tischler V, Michels S, Dahmen I, Brägelmann J, Menon R, Heuckmann JM, George J, Ansén S, Sos ML, Soltermann A, Peifer M, Wolf J, Büttner R, Thomas RK. Mechanisms of Primary Drug Resistance in FGFR1-Amplified Lung Cancer. Clin Cancer Res 2017; 23:5527-5536.
    • FGFR1
    • R2 Cowell JK, Qin H, Hu T, Wu Q, Bhole A, Ren M. Mutation in the FGFR1 tyrosine kinase domain or inactivation of PTEN is associated with acquired resistance to FGFR inhibitors in FGFR1-driven leukemia/lymphomas. Int J Cancer 2017; 141:1822-1829.
    • FGFR3
    • R2 Pal SK, Rosenberg JE, Hoffman-Censits JH, Berger R, Quinn DI, Galsky MD, Wolf J, Dittrich C, Keam B, Delord JP, Schellens JHM, Gravis G, Medioni J, Maroto P, Sriuranpong V, Charoentum C, Burris HA, Grünwald V, Petrylak D, Vaishampayan U, Gez E, De Giorgi U, Lee JL, Voortman J, Gupta S, Sharma S, Mortazavi A, Vaughn DJ, Isaacs R, Parker K, Chen X, Yu K, Porter D, Graus Porta D, Bajorin DF. Efficacy of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Inhibitor, in Patients with Previously Treated Advanced Urothelial Carcinoma with FGFR3 Alterations. Cancer Discov 2018; 8:812-821.
    • FGFR2
    • R2 Krook MA, Lenyo A, Wilberding M, Barker H, Dantuono M, Bailey KM, Chen HZ, Reeser JW, Wing MR, Miya J, Samorodnitsky E, Smith AM, Dao T, Martin DM, Ciombor KK, Hays J, Freud AG, Roychowdhury S. Efficacy of FGFR Inhibitors and Combination Therapies for Acquired Resistance in FGFR2-Fusion Cholangiocarcinoma. Mol Cancer Ther 2020; 19:847-857.
    • R2 Sootome H, Fujita H, Ito K, Ochiiwa H, Fujioka Y, Ito K, Miura A, Sagara T, Ito S, Ohsawa H, Otsuki S, Funabashi K, Yashiro M, Matsuo K, Yonekura K, Hirai H. Futibatinib Is a Novel Irreversible FGFR 1-4 Inhibitor That Shows Selective Antitumor Activity against FGFR-Deregulated Tumors. Cancer Res 2020; 80:4986-4997.
    • FGFR2
    • 2 Javle MM, Sadeghi S, El-Khoueiry AB, Goyal L, Philip PA, Kelley RK, Borbath I, Macarulla T, Yong W, Tanasanvimon S, Pande A, Li G, Howland M, Berman C, Abou-Alfa GK. A retrospective analysis of post second-line chemotherapy treatment outcomes for patients with advanced or metastatic cholangiocarcinoma and FGFR2 fusions. J Clin Oncol 2020; 38(15_suppl): 4591-4591.
    • 2 Javle MM, Roychowdhury S, Kelley RK, Sadeghi S, Macarulla T, Waldschmidt DT, Goyal L, Borbath I, El-Khoueiry AB, Yong W, Philip PA, Bitzer M, Tanasanvimon S, Li A, Pande A, Shepherd SP, Moran S, Abou-Alfa GK. Final results from a phase II study of infigratinib (BGJ398), an FGFR-selective tyrosine kinase inhibitor, in patients with previously treated advanced cholangiocarcinoma harboring an FGFR2 gene fusion or rearrangement. J Clin Oncol 2021; 39(3_suppl): 265-265.
    • FGFR3
    • 3 Dizman N, Rosenberg JE, Hoffman-Censits JH, Quinn DI, Petrylak DP, Galsky MD, Vaishampayan UN, Giorgi UD, Gupta S, Burris HA, Soifer HS, Li G, Dambkowski CL, Moran S, Ye Y, Daneshmand S, Bajorin DF, Pal SK. Infigratinib in upper tract urothelial carcinoma vs urothelial carcinoma of the bladder and association with comprehensive genomic profiling/cell-free DNA results. J Clin Oncol 2019; 37(15_suppl): 4510-4510.
    • 3 Pal SK, Rosenberg JE, Hoffman-Censits JH, Berger R, Quinn DI, Galsky MD, Wolf J, Dittrich C, Keam B, Delord JP, Schellens JHM, Gravis G, Medioni J, Maroto P, Sriuranpong V, Charoentum C, Burris HA, Grünwald V, Petrylak D, Vaishampayan U, Gez E, De Giorgi U, Lee JL, Voortman J, Gupta S, Sharma S, Mortazavi A, Vaughn DJ, Isaacs R, Parker K, Chen X, Yu K, Porter D, Graus Porta D, Bajorin DF. Efficacy of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Inhibitor, in Patients with Previously Treated Advanced Urothelial Carcinoma with FGFR3 Alterations. Cancer Discov 2018; 8:812-821.
    • FGFR1
    • 4 Javle M, Kelley R, Roychowdhury S, Weiss K, Abou-Alfa G, Macarulla T, Sadeghi S, Waldschmidt D, Zhu A, Goyal L, Borad M, Yong W, Borbath I, El-Khoueiry A, Philip P, Moran S, Ye Y, Ising M, Lewis N, Bekaii-Saab T. Updated results from a phase II study of infigratinib (BGJ398), a selective pan-FGFR kinase inhibitor, in patients with previously treated advanced cholangiocarcinoma containing FGFR2 fusions. Ann Oncol; 10.1093/annonc/mdy424.030
    • FGFR1, FGFR2, FGFR3
    • 4 Infigratinib for the Treatment of Advanced or Metastatic Solid Tumors in Patients With FGFR Gene Mutations [NCT04233567]
    • FGFR1
    • 4 Nogova L, Sequist LV, Perez Garcia JM, Andre F, Delord JP, Hidalgo M, Schellens JH, Cassier PA, Camidge DR, Schuler M, Vaishampayan U, Burris H, Tian GG, Campone M, Wainberg ZA, Lim WT, LoRusso P, Shapiro GI, Parker K, Chen X, Choudhury S, Ringeisen F, Graus-Porta D, Porter D, Isaacs R, Buettner R, Wolf J. Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study. J Clin Oncol 2017; 35:157-165.
    • Ipatasertib
    • AKT1, AKT2, AKT3
    • 4 Tumor-Agnostic Precision Immuno-Oncology and Somatic Targeting Rational for You (TAPISTRY) Platform Study [NCT04589845]
    • PIK3CA, PTEN
    • 4 Lin J, Sampath D, Nannini MA, Lee BB, Degtyarev M, Oeh J, Savage H, Guan Z, Hong R, Kassees R, Lee LB, Risom T, Gross S, Liederer BM, Koeppen H, Skelton NJ, Wallin JJ, Belvin M, Punnoose E, Friedman LS, Lin K. Targeting activated Akt with GDC-0068, a novel selective Akt inhibitor that is efficacious in multiple tumor models. Clin Cancer Res 2013; 19:1760-72.
    • Ipatasertib + Abiraterone
    • PTEN
    • 2 Bono Jd, Bracarda S, Sternberg C, Chi K, Olmos D, Sandhu S, Massard C, Matsubara N, Alekseev B, Gafanov R, Parnis F, Jr. GB, Corrales L, Borre M, Alves GV, Garcia J, Harle-Yge M, Chen G, Wongchenko M, Sweeney C. LBA4 IPATential150: Phase III study of ipatasertib (ipat) plus abiraterone (abi) vs placebo (pbo) plus abi in metastatic castration-resistant prostate cancer (mCRPC). Ann Oncol 2020; 31 (4): S1153. 10.1016/j.annonc.2020.08.2250
    • 2 Sweeney C, Bracarda S, Sternberg CN, Chi KN, Olmos D, Sandhu S, Massard C, Matsubara N, Alekseev B, Parnis F, Atduev V, Buchschacher GL Jr, Gafanov R, Corrales L, Borre M, Stroyakovskiy D, Alves GV, Bournakis E, Puente J, Harle-Yge ML, Gallo J, Chen G, Hanover J, Wongchenko MJ, Garcia J, de Bono JS. Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150): a multicentre, randomised, double-blind, phase 3 trial. Lancet 2021; 398:131-142.
    • Ipatasertib + FOLFOX
    • PIK3CA, PTEN
    • R2 Bang YJ, Kang YK, Ng M, Chung HC, Wainberg ZA, Gendreau S, Chan WY, Xu N, Maslyar D, Meng R, Chau I, Ajani JA. A phase II, randomised study of mFOLFOX6 with or without the Akt inhibitor ipatasertib in patients with locally advanced or metastatic gastric or gastroesophageal junction cancer. Eur J Cancer 2019; 108:17-24.
    • Ipatasertib + Paclitaxel
    • AKT1, PIK3CA, PTEN
    • 3 Kim SB, Dent R, Im SA, Espié M, Blau S, Tan AR, Isakoff SJ, Oliveira M, Saura C, Wongchenko MJ, Kapp AV, Chan WY, Singel SM, Maslyar DJ, Baselga J; LOTUS investigators. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol 2017; 18:1360-1372.
    • AKT1, PIK3CA, PTEN
    • 4 Turner N, Dent R, O'Shaughnessy J, Kim S, Isakoff S, Barrios C, Saji S, Bondarenko I, Nowecki Z, Lian Q, Reilly S, Hinton H, Wongchenko M, Mani A, Oliveira M. 283MO Ipatasertib (IPAT) + paclitaxel (PAC) for PIK3CA/AKT1/PTEN-altered hormone receptor-positive (HR+) HER2-negative advanced breast cancer (aBC): Primary results from Cohort B of the IPATunity130 randomised phase III trial. Ann Oncol 2020; 31 (4): S354. 10.1016/j.annonc.2020.08.385
    • Ipilimumab + Nivolumab
    • Microsatellite Instability, Mismatch repair
    • 2 Overman MJ, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Svrcek M, Moss RA, Ledeine JM, Cao ZA, Kamble S, Kopetz S, André T. Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol 2018; 36:773-779.
    • 2 Lenz HJ, Van Cutsem E, Luisa Limon M, Wong KYM, Hendlisz A, Aglietta M, García-Alfonso P, Neyns B, Luppi G, Cardin DB, Dragovich T, Shah U, Abdullaev S, Gricar J, Ledeine JM, Overman MJ, Lonardi S. First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study. J Clin Oncol 2021 Oct 12:JCO2101015. [Epub ahead of print]
    • Ipilimumab + Nivolumab + Carboplatin + Paclitaxel
    • Tumour Mutational Burden
    • Ipilimumab + Nivolumab + Carboplatin + Pemetrexed
    • Tumour Mutational Burden
    • Ipilimumab + Nivolumab + Cisplatin + Pemetrexed
    • Tumour Mutational Burden
    • Isatuximab-irfc + Pomalidomide + Dexamethasone
    • CD38
    • 1B Attal M, Richardson PG, Rajkumar SV, San-Miguel J, Beksac M, Spicka I, Leleu X, Schjesvold F, Moreau P, Dimopoulos MA, Huang JS, Minarik J, Cavo M, Prince HM, Macé S, Corzo KP, Campana F, Le-Guennec S, Dubin F, Anderson KC; ICARIA-MM study group. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet 2019; 394:2096-2107.
    • Itraconazole
    • PTCH1, SMO
    • 4 Kim J, Aftab BT, Tang JY, Kim D, Lee AH, Rezaee M, Kim J, Chen B, King EM, Borodovsky A, Riggins GJ, Epstein EH Jr, Beachy PA, Rudin CM. Itraconazole and arsenic trioxide inhibit Hedgehog pathway activation and tumor growth associated with acquired resistance to smoothened antagonists. Cancer Cell 2013; 23:23-34.
    • Ivosidenib
    • BRAF, FLT3, IDH1, KIT, KRAS, NF1, PTPN11
    • R2 Choe S, Wang H, DiNardo CD, Stein EM, de Botton S, Roboz GJ, Altman JK, Mims AS, Watts JM, Pollyea DA, Fathi AT, Tallman MS, Kantarjian HM, Stone RM, Quek L, Konteatis Z, Dang L, Nicolay B, Nejad P, Liu G, Zhang V, Liu H, Goldwasser M, Liu W, Marks K, Bowden C, Biller SA, Attar EC, Wu B. Molecular mechanisms mediating relapse following ivosidenib monotherapy in IDH1-mutant relapsed or refractory AML. Blood Adv 2020; 4:1894-1905.
    • IDH1
    • R2 Assessing acquired resistance to IDH1 inhibitor therapy by full-exon IDH1 sequencing and structural modeling. Print 2021 Apr. Cold Spring Harb Mol Case Stud 2021; 7(2). pii: a006007.
    • IDH1
    • 2 DiNardo CD, Stein EM, de Botton S, Roboz GJ, Altman JK, Mims AS, Swords R, Collins RH, Mannis GN, Pollyea DA, Donnellan W, Fathi AT, Pigneux A, Erba HP, Prince GT, Stein AS, Uy GL, Foran JM, Traer E, Stuart RK, Arellano ML, Slack JL, Sekeres MA, Willekens C, Choe S, Wang H, Zhang V, Yen KE, Kapsalis SM, Yang H, Dai D, Fan B, Goldwasser M, Liu H, Agresta S, Wu B, Attar EC, Tallman MS, Stone RM, Kantarjian HM. Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML. N Engl J Med 2018; 378:2386-2398.
    • 2 Abou-Alfa GK, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, Cleary JM, Catenacci DV, Borad MJ, Bridgewater J, Harris WP, Murphy AG, Oh DY, Whisenant J, Lowery MA, Goyal L, Shroff RT, El-Khoueiry AB, Fan B, Wu B, Chamberlain CX, Jiang L, Gliser C, Pandya SS, Valle JW, Zhu AX. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 2020; 21:796-807.
    • IDH1
    • 4 Tap WD, Villalobos VM, Cote GM, Burris H, Janku F, Mir O, Beeram M, Wagner AJ, Jiang L, Wu B, Choe S, Yen K, Gliser C, Fan B, Agresta S, Pandya SS, Trent JC. Phase I Study of the Mutant IDH1 Inhibitor Ivosidenib: Safety and Clinical Activity in Patients With Advanced Chondrosarcoma. J Clin Oncol 2020; 38:1693-1701.
    • 4 Mellinghoff IK, Ellingson BM, Touat M, Maher E, De La Fuente MI, Holdhoff M, Cote GM, Burris H, Janku F, Young RJ, Huang R, Jiang L, Choe S, Fan B, Yen K, Lu M, Bowden C, Steelman L, Pandya SS, Cloughesy TF, Wen PY. Ivosidenib in Isocitrate Dehydrogenase 1-Mutated Advanced Glioma. J Clin Oncol 2020 Jun 12:JCO1903327. [Epub ahead of print]
    • Ivosidenib + Azacitidine
    • IDH1
    • 2 Montesinos P, Recher C, Vives S, Zarzycka E, Wang J, Bertani G, Heuser M, Calado RT, Schuh AC, Yeh SP, Daigle SR, Hui J, Pandya SS, Gianolio DA, de Botton S, Döhner H. Ivosidenib and Azacitidine in IDH1-Mutated Acute Myeloid Leukemia. N Engl J Med 2022; 386:1519-1531.
    • IDH1
    • 3 DiNardo CD, Stein AS, Stein EM, Fathi AT, Frankfurt O, Schuh AC, Döhner H, Martinelli G, Patel PA, Raffoux E, Tan P, Zeidan AM, de Botton S, Kantarjian HM, Stone RM, Frattini MG, Lersch F, Gong J, Gianolio DA, Zhang V, Franovic A, Fan B, Goldwasser M, Daigle S, Choe S, Wu B, Winkler T, Vyas P. Mutant Isocitrate Dehydrogenase 1 Inhibitor Ivosidenib in Combination With Azacitidine for Newly Diagnosed Acute Myeloid Leukemia. J Clin Oncol 2021; 39:57-65.
    • immune checkpoint blockade,CTLA-4 targeting
    • Mismatch repair
    • 4 Marcus L, Lemery SJ, Pazdur PKaR. FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors Clin Cancer Res July 1 2019 (25) (13) 3753-3758; DOI: 10.1158/1078-0432.CCR-18-4070
    • 4 Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 2015; 372:2509-20.
    • Microsatellite Instability
    • 4 Marcus L, Lemery SJ, Keegan P, Pazdur R. FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors. Clin Cancer Res 2019; 25:3753-3758.
    • Mismatch repair
    • 4 Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, Geva R, Gottfried M, Penel N, Hansen AR, Piha-Paul SA, Doi T, Gao B, Chung HC, Lopez-Martin J, Bang YJ, Frommer RS, Shah M, Ghori R, Joe AK, Pruitt SK, Diaz LA Jr. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol 2020; 38:1-10.
    • immune checkpoint blockade,PD-1 targeting
    • Mismatch repair
    • 4 Marcus L, Lemery SJ, Pazdur PKaR. FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors Clin Cancer Res July 1 2019 (25) (13) 3753-3758; DOI: 10.1158/1078-0432.CCR-18-4070
    • 4 Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 2015; 372:2509-20.
    • Tumour Mutational Burden
    • 4 Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, Barron DA, Zehir A, Jordan EJ, Omuro A, Kaley TJ, Kendall SM, Motzer RJ, Hakimi AA, Voss MH, Russo P, Rosenberg J, Iyer G, Bochner BH, Bajorin DF, Al-Ahmadie HA, Chaft JE, Rudin CM, Riely GJ, Baxi S, Ho AL, Wong RJ, Pfister DG, Wolchok JD, Barker CA, Gutin PH, Brennan CW, Tabar V, Mellinghoff IK, DeAngelis LM, Ariyan CE, Lee N, Tap WD, Gounder MM, D'Angelo SP, Saltz L, Stadler ZK, Scher HI, Baselga J, Razavi P, Klebanoff CA, Yaeger R, Segal NH, Ku GY, DeMatteo RP, Ladanyi M, Rizvi NA, Berger MF, Riaz N, Solit DB, Chan TA, Morris LGT. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet 2019; 51:202-206.
    • Microsatellite Instability
    • 4 Marcus L, Lemery SJ, Keegan P, Pazdur R. FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors. Clin Cancer Res 2019; 25:3753-3758.
    • Mismatch repair
    • 4 Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, Geva R, Gottfried M, Penel N, Hansen AR, Piha-Paul SA, Doi T, Gao B, Chung HC, Lopez-Martin J, Bang YJ, Frommer RS, Shah M, Ghori R, Joe AK, Pruitt SK, Diaz LA Jr. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol 2020; 38:1-10.
    • immune checkpoint blockade,PD-L1 targeting
    • Mismatch repair
    • 4 Marcus L, Lemery SJ, Pazdur PKaR. FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors Clin Cancer Res July 1 2019 (25) (13) 3753-3758; DOI: 10.1158/1078-0432.CCR-18-4070
    • 4 Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 2015; 372:2509-20.
    • Tumour Mutational Burden
    • 4 Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, Barron DA, Zehir A, Jordan EJ, Omuro A, Kaley TJ, Kendall SM, Motzer RJ, Hakimi AA, Voss MH, Russo P, Rosenberg J, Iyer G, Bochner BH, Bajorin DF, Al-Ahmadie HA, Chaft JE, Rudin CM, Riely GJ, Baxi S, Ho AL, Wong RJ, Pfister DG, Wolchok JD, Barker CA, Gutin PH, Brennan CW, Tabar V, Mellinghoff IK, DeAngelis LM, Ariyan CE, Lee N, Tap WD, Gounder MM, D'Angelo SP, Saltz L, Stadler ZK, Scher HI, Baselga J, Razavi P, Klebanoff CA, Yaeger R, Segal NH, Ku GY, DeMatteo RP, Ladanyi M, Rizvi NA, Berger MF, Riaz N, Solit DB, Chan TA, Morris LGT. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet 2019; 51:202-206.
    • Microsatellite Instability
    • 4 Marcus L, Lemery SJ, Keegan P, Pazdur R. FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors. Clin Cancer Res 2019; 25:3753-3758.
    • Mismatch repair
    • 4 Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, Geva R, Gottfried M, Penel N, Hansen AR, Piha-Paul SA, Doi T, Gao B, Chung HC, Lopez-Martin J, Bang YJ, Frommer RS, Shah M, Ghori R, Joe AK, Pruitt SK, Diaz LA Jr. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol 2020; 38:1-10.
    • immune checkpoint blockade,PD-L1 targeting
    • CD274
    • 4 Sorscher S, Goodman M, Ramkissoon S. Acquired Resistance to Immune Checkpoint Inhibitor Therapy Through Outgrowth of Cells Lacking CD274 and PDCD1LG2 Amplification. JCO Prec Oncol 2018; - published online May 9, 2018
    • 4 Gröschel S, Bommer M, Hutter B, Budczies J, Bonekamp D, Heining C, Horak P, Fröhlich M, Uhrig S, Hübschmann D, Geörg C, Richter D, Pfarr N, Pfütze K, Wolf S, Schirmacher P, Jäger D, von Kalle C, Brors B, Glimm H, Weichert W, Stenzinger A, Fröhling S. Integration of genomics and histology revises diagnosis and enables effective therapy of refractory cancer of unknown primary with PDL1 amplification. Cold Spring Harb Mol Case Stud 2016; 2:a001180.
    • 4 Ikeda S, Goodman AM, Cohen PR, Jensen TJ, Ellison CK, Frampton G, Miller V, Patel SP, Kurzrock R. Metastatic basal cell carcinoma with amplification of PD-L1: exceptional response to anti-PD1 therapy. NPJ Genom Med 2016;1. pii: 16037.
    • 4 Goodman AM, Piccioni D, Kato S, Boichard A, Wang HY, Frampton G, Lippman SM, Connelly C, Fabrizio D, Miller V, Sicklick JK, Kurzrock R. Prevalence of PDL1 Amplification and Preliminary Response to Immune Checkpoint Blockade in Solid Tumors. JAMA Oncol 2018; 4:1237-1244.
    • J
    • JAB-21822
    • KRAS
    • 4 . . [DOI:]
    • JQ1
    • SMO
    • 4 Tang Y, Gholamin S, Schubert S, Willardson MI, Lee A, Bandopadhayay P, Bergthold G, Masoud S, Nguyen B, Vue N, Balansay B, Yu F, Oh S, Woo P, Chen S, Ponnuswami A, Monje M, Atwood SX, Whitson RJ, Mitra S, Cheshier SH, Qi J, Beroukhim R, Tang JY, Wechsler-Reya R, Oro AE, Link BA, Bradner JE, Cho YJ. Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition. Nat Med 2014; 20:732-40.
    • SUZ12
    • 4 De Raedt T, Beert E, Pasmant E, Luscan A, Brems H, Ortonne N, Helin K, Hornick JL, Mautner V, Kehrer-Sawatzki H, Clapp W, Bradner J, Vidaud M, Upadhyaya M, Legius E, Cichowski K. PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature 2014; 514:247-51.
    • KDM6A
    • 4 Andricovich J, Perkail S, Kai Y, Casasanta N, Peng W, Tzatsos A. Loss of KDM6A Activates Super-Enhancers to Induce Gender-Specific Squamous-like Pancreatic Cancer and Confers Sensitivity to BET Inhibitors. Cancer Cell 2018; 33:512-526.e8.
    • ARID1A
    • 4 Berns K, Caumanns JJ, Hijmans EM, Gennissen AMC, Severson TM, Evers B, Wisman GBA, Jan Meersma G, Lieftink C, Beijersbergen RL, Itamochi H, van der Zee AGJ, de Jong S, Bernards R. ARID1A mutation sensitizes most ovarian clear cell carcinomas to BET inhibitors. Oncogene 2018; 37:4611-4625.
    • EIF1AX, EIF1AX+NRAS
    • 4 Krishnamoorthy GP, Davidson NR, Leach SD, Zhao Z, Lowe SW, Lee G, Landa I, Nagarajah J, Saqcena M, Singh K, Wendel HG, Dogan S, Tamarapu PP, Blenis J, Ghossein RA, Knauf JA, Rätsch G, Fagin JA. EIF1AX and RAS Mutations Cooperate to Drive Thyroid Tumorigenesis through ATF4 and c-MYC. Cancer Discov 2019; 9:264-281.
    • K
    • KU-55933
    • FANCG
    • 4 Kennedy RD, Chen CC, Stuckert P, Archila EM, De la Vega MA, Moreau LA, Shimamura A, D'Andrea AD. Fanconi anemia pathway-deficient tumor cells are hypersensitive to inhibition of ataxia telangiectasia mutated. J Clin Invest 2007; 117:1440-9.
    • L
    • LOP628
    • KIT
    • 4 Abrams T, Connor A, Fanton C, Cohen SB, Huber T, Miller K, Hong EE, Niu X, Kline J, Ison-Dugenny M, Harris S, Walker D, Krauser K, Galimi F, Wang Z, Ghoddusi M, Mansfield K, Lee-Hoeflich ST, Holash J, Pryer N, Kluwe W, Ettenberg SA, Sellers WR, Lees E, Kwon P, Abraham JA, Schleyer SC. Preclinical Antitumor Activity of a Novel Anti-c-KIT Antibody-Drug Conjugate against Mutant and Wild-type c-KIT-Positive Solid Tumors. Clin Cancer Res 2018; 24:4297-4308.
    • LOXO-783
    • PIK3CA
    • 4 A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors [NCT05307705]
    • LTT462
    • HRAS, KRAS, NF1, NRAS, PTPN11
    • 4 Pant S, Bendell JC, Sullivan RJ, Shapiro G, Millward M, Mi G, Yuen E, Willard MD, Wang D, Joseph S, McMillen WT, Bhagwat SV, Tiu RV, Patel MR. A phase I dose escalation (DE) study of ERK inhibitor, LY3214996, in advanced (adv) cancer (CA) patients (pts). J Clin Oncol 2019; 37(15_suppl): 3001-3001.
    • 4 Sullivan RJ, Infante JR, Janku F, Wong DJL, Sosman JA, Keedy V, Patel MR, Shapiro GI, Mier JW, Tolcher AW, Wang-Gillam A, Sznol M, Flaherty K, Buchbinder E, Carvajal RD, Varghese AM, Lacouture ME, Ribas A, Patel SP, DeCrescenzo GA, Emery CM, Groover AL, Saha S, Varterasian M, Welsch DJ, Hyman DM, Li BT. First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study. Cancer Discov 2018; 8:184-195.
    • 4 Smalley I, Smalley KSM. ERK Inhibition: A New Front in the War against MAPK Pathway-Driven Cancers? Cancer Discov 2018; 8:140-142.
    • LY2874455
    • FRS2
    • 4 Hanes R, Munthe E, Grad I, Han J, Karlsen I, McCormack E, Meza-Zepeda LA, Stratford EW, Myklebost O. Preclinical Evaluation of the Pan-FGFR Inhibitor LY2874455 in FRS2-Amplified Liposarcoma. Cells 2019; 8(2). pii: E189.
    • LY3009120
    • BRAF
    • R2 Chen SH, Zhang Y, Van Horn RD, Yin T, Buchanan S, Yadav V, Mochalkin I, Wong SS, Yue YG, Huber L, Conti I, Henry JR, Starling JJ, Plowman GD, Peng SB. Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120. Cancer Discov 2016; 6:300-15.
    • BRAF
    • 4 Chen SH, Zhang Y, Van Horn RD, Yin T, Buchanan S, Yadav V, Mochalkin I, Wong SS, Yue YG, Huber L, Conti I, Henry JR, Starling JJ, Plowman GD, Peng SB. Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120. Cancer Discov 2016; 6:300-15.
    • RAF1
    • 4 Jain P, Fierst TM, Han HJ, Smith TE, Vakil A, Storm PB, Resnick AC, Waanders AJ. CRAF gene fusions in pediatric low-grade gliomas define a distinct drug response based on dimerization profiles. Oncogene 2017; 36:6348-6358.
    • BRAF
    • 4 Yao Z, Gao Y, Su W, Yaeger R, Tao J, Na N, Zhang Y, Zhang C, Rymar A, Tao A, Timaul NM, Mcgriskin R, Outmezguine NA, Zhao H, Chang Q, Qeriqi B, Barbacid M, de Stanchina E, Hyman DM, Bollag G, Rosen N. RAF inhibitor PLX8394 selectively disrupts BRAF dimers and RAS-independent BRAF-mutant-driven signaling. Nat Med 2019; 25:284-291.
    • LY3023414
    • AKT1, PIK3CA, PIK3R1, PTEN
    • R2 Rubinstein MM, Hyman DM, Caird I, Won H, Soldan K, Seier K, Iasonos A, Tew WP, O'Cearbhaill RE, Grisham RN, Hensley ML, Troso-Sandoval T, Sabbatini P, Guillen J, Selcuklu SD, Zimel C, Torrisi J, Aghajanian C, Makker V. Phase 2 study of LY3023414 in patients with advanced endometrial cancer harboring activating mutations in the PI3K pathway. Cancer 2020; 126:1274-1282.
    • LY3143921
    • TP53
    • 4 . . [DOI:]
    • LY3214996
    • BRAF
    • 4 Shripad V. Bhagwat, William T. McMillen, Shufen Cai, Baohui Zhao, Matthew Whitesell, Lisa Kindler, Robert S. Flack, Wenjuan Wu, Karen Huss, Bryan Anderson, Xiu-Juan Yuan, Susan Jaken, Denis McCann, Brian Mathes, Andrew J. Dropsey, Jason Manro, Jennie Walgren, Eunice Yuen, Xueqian Gong, Michael J. Rodriguez, Jianping Huang, Ramon V. Tiu, Sajan Joseph, Sheng-Bin Peng. Discovery of LY3214996, a selective and novel ERK1/2 inhibitor with potent antitumor activities in cancer models with MAPK pathway alterations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4973. doi:10.1158/1538-7445.AM2017-4973
    • BRAF, HRAS, KRAS, NF1, NRAS, PTPN11
    • 4 Pant S, Bendell JC, Sullivan RJ, Shapiro G, Millward M, Mi G, Yuen E, Willard MD, Wang D, Joseph S, McMillen WT, Bhagwat SV, Tiu RV, Patel MR. A phase I dose escalation (DE) study of ERK inhibitor, LY3214996, in advanced (adv) cancer (CA) patients (pts). J Clin Oncol 2019; 37(15_suppl): 3001-3001.
    • BRAF
    • 4 Morris EJ, Jha S, Restaino CR, Dayananth P, Zhu H, Cooper A, Carr D, Deng Y, Jin W, Black S, Long B, Liu J, Dinunzio E, Windsor W, Zhang R, Zhao S, Angagaw MH, Pinheiro EM, Desai J, Xiao L, Shipps G, Hruza A, Wang J, Kelly J, Paliwal S, Gao X, Babu BS, Zhu L, Daublain P, Zhang L, Lutterbach BA, Pelletier MR, Philippar U, Siliphaivanh P, Witter D, Kirschmeier P, Bishop WR, Hicklin D, Gilliland DG, Jayaraman L, Zawel L, Fawell S, Samatar AA. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discov 2013; 3:742-50.
    • HRAS, KRAS, NF1, NRAS, PTPN11
    • 4 Sullivan RJ, Infante JR, Janku F, Wong DJL, Sosman JA, Keedy V, Patel MR, Shapiro GI, Mier JW, Tolcher AW, Wang-Gillam A, Sznol M, Flaherty K, Buchbinder E, Carvajal RD, Varghese AM, Lacouture ME, Ribas A, Patel SP, DeCrescenzo GA, Emery CM, Groover AL, Saha S, Varterasian M, Welsch DJ, Hyman DM, Li BT. First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study. Cancer Discov 2018; 8:184-195.
    • 4 Smalley I, Smalley KSM. ERK Inhibition: A New Front in the War against MAPK Pathway-Driven Cancers? Cancer Discov 2018; 8:140-142.
    • LY3295668
    • MYCN
    • 4 DuBois SG, Kremer JD, Wilde BD, Jacobsen C, Aerts I, Mosse YP, Maris JM, Lithio A, Gosberg A, Banks C, Tate C, Dowless M, Gong X, Stancato L, Bell-McGuinn KM, Park JR, Pearson AD, Marachelian A. A phase I study of Aurora kinase A inhibitor LY3295668 erbumine as a single agent and in combination in patients with relapsed/refractory neuroblastoma. J Clin Oncol 2020; 38(15_suppl):
    • 4 A Study of LY3295668 Erbumine in Participants With Relapsed/Refractory Neuroblastoma [NCT04106219]
    • RB1
    • 4 Gong X, Du J, Parsons SH, Merzoug FF, Webster Y, Iversen PW, Chio LC, Van Horn RD, Lin X, Blosser W, Han B, Jin S, Yao S, Bian H, Ficklin C, Fan L, Kapoor A, Antonysamy S, Mc Nulty AM, Froning K, Manglicmot D, Pustilnik A, Weichert K, Wasserman SR, Dowless M, Marugán C, Baquero C, Lallena MJ, Eastman SW, Hui YH, Dieter MZ, Doman T, Chu S, Qian HR, Ye XS, Barda DA, Plowman GD, Reinhard C, Campbell RM, Henry JR, Buchanan SG. Aurora A Kinase Inhibition Is Synthetic Lethal with Loss of the RB1 Tumor Suppressor Gene. Cancer Discov 2019; 9:248-263.
    • LY3537982
    • KRAS
    • 4 Sheng-Bin Peng, Chong Si, Youyan Zhang, Robert D. Van Horn, Xi Lin, Xueqian Gong, Lysiane Huber, Gregory Donoho, Carmen Curtis, John M. Strelow, Wayne P. Bocchinfuso, Deqi Guo, Serge L. Boulet, David Barda, Danalyn Manglicmot, Melbert-Brian D. Saflor, Jing Wang, Junpeng Xiao, Michael J. Chalmers, Lee Burns, Ryan J. Linder, Bradley L. Ackermann, Paul D. Cornwell, Lian Zhou, Denis McCann, James Henry. Preclinical characterization of LY3537982, a novel, highly selective and potent KRAS-G12C inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1259.
    • Lanreotide
    • SSTR2
    • 1 Caplin ME, Pavel M, Ćwikła JB, Phan AT, Raderer M, Sedláčková E, Cadiot G, Wolin EM, Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Blumberg J, Ruszniewski P; CLARINET Investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med 2014; 371:224-33.
    • Lapatinib
    • ERBB2
    • R2 Jamunarani Veeraraghavan, Ragini Mistry, Sarmistha Nanda, Vidyalakshmi Sethunath, Martin Shea, Tamika Mitchell, Meenakshi Anurag, Michael A. Mancini, Fabio Stossi, C. Kent Osborne, Mothaffar F. Rimawi, Rachel Schiff. HER2 L755S mutation is acquired upon resistance to lapatinib and neratinib and confers cross-resistance to tucatinib and trastuzumab in HER2-positive breast cancer cell models [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD3-09.
    • EGFR, PTEN
    • R2 Thiessen B, Stewart C, Tsao M, Kamel-Reid S, Schaiquevich P, Mason W, Easaw J, Belanger K, Forsyth P, McIntosh L, Eisenhauer E. A phase I/II trial of GW572016 (lapatinib) in recurrent glioblastoma multiforme: clinical outcomes, pharmacokinetics and molecular correlation. Cancer Chemother Pharmacol 2010; 65:353-61.
    • ERBB2
    • R2 Bose R, Kavuri SM, Searleman AC, Shen W, Shen D, Koboldt DC, Monsey J, Goel N, Aronson AB, Li S, Ma CX, Ding L, Mardis ER, Ellis MJ. Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer Discov 2013; 3:224-37.
    • R2 Powles T, Huddart RA, Elliott T, Sarker SJ, Ackerman C, Jones R, Hussain S, Crabb S, Jagdev S, Chester J, Hilman S, Beresford M, Macdonald G, Santhanam S, Frew JA, Stockdale A, Hughes S, Berney D, Chowdhury S. Phase III, Double-Blind, Randomized Trial That Compared Maintenance Lapatinib Versus Placebo After First-Line Chemotherapy in Patients With Human Epidermal Growth Factor Receptor 1/2-Positive Metastatic Bladder Cancer. J Clin Oncol 2017; 35:48-55.
    • ERBB3
    • R2 Mishra R, Alanazi S, Yuan L, Solomon T, Thaker TM, Jura N, Garrett JT. Activating HER3 mutations in breast cancer. Oncotarget 2018; 9:27773-27788. eCollection 2018 Jun 12.
    • ERBB2
    • R2 Nagano M, Kohsaka S, Ueno T, Kojima S, Saka K, Iwase H, Kawazu M, Mano H. High-Throughput Functional Evaluation of Variants of Unknown Significance in ERBB2. Clin Cancer Res 2018; 24:5112-5122.
    • R2 Robichaux JP, Elamin YY, Vijayan RSK, Nilsson MB, Hu L, He J, Zhang F, Pisegna M, Poteete A, Sun H, Li S, Chen T, Han H, Negrao MV, Ahnert JR, Diao L, Wang J, Le X, Meric-Bernstam F, Routbort M, Roeck B, Yang Z, Raymond VM, Lanman RB, Frampton GM, Miller VA, Schrock AB, Albacker LA, Wong KK, Cross JB, Heymach JV. Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 Activity. Cancer Cell 2019; 36:444-457.e7.
    • R2 Gaibar M, Beltrán L, Romero-Lorca A, Fernández-Santander A, Novillo A. Somatic Mutations in HER2 and Implications for Current Treatment Paradigms in HER2-Positive Breast Cancer. J Oncol 2020; 2020:6375956. eCollection 2020.
    • ERBB2
    • 4 Jia Z, Liang N, Wang Y, Wang Y, Ye J, Wang W, Li B, Han-Zhang H, Zhao J, Zhang X, Peng F, Chen F, Chen X, Lu Y, Ying S, Dp W, Zhang X, Ma C, Lai L, Ma S, Institute UCH&, Tianjin , Center CXAR, Beijing , XtalPi C, Shenzhen , China . Clinical management of lung adenocarcinoma patients with HER2 V659E mutation. J Clin Oncol 2020; 38(15_suppl):
    • EGFR
    • 4 Vivanco I, Robins HI, Rohle D, Campos C, Grommes C, Nghiemphu PL, Kubek S, Oldrini B, Chheda MG, Yannuzzi N, Tao H, Zhu S, Iwanami A, Kuga D, Dang J, Pedraza A, Brennan CW, Heguy A, Liau LM, Lieberman F, Yung WK, Gilbert MR, Reardon DA, Drappatz J, Wen PY, Lamborn KR, Chang SM, Prados MD, Fine HA, Horvath S, Wu N, Lassman AB, DeAngelis LM, Yong WH, Kuhn JG, Mischel PS, Mehta MP, Cloughesy TF, Mellinghoff IK. Differential sensitivity of glioma- versus lung cancer-specific EGFR mutations to EGFR kinase inhibitors. Cancer Discov 2012; 2:458-71.
    • ERBB3
    • 4 Jaiswal BS, Kljavin NM, Stawiski EW, Chan E, Parikh C, Durinck S, Chaudhuri S, Pujara K, Guillory J, Edgar KA, Janakiraman V, Scholz RP, Bowman KK, Lorenzo M, Li H, Wu J, Yuan W, Peters BA, Kan Z, Stinson J, Mak M, Modrusan Z, Eigenbrot C, Firestein R, Stern HM, Rajalingam K, Schaefer G, Merchant MA, Sliwkowski MX, de Sauvage FJ, Seshagiri S. Oncogenic ERBB3 mutations in human cancers. Cancer Cell 2013; 23:603-17.
    • ERBB2
    • 4 de Martino M, Zhuang D, Klatte T, Rieken M, Rouprêt M, Xylinas E, Clozel T, Krzywinski M, Elemento O, Shariat SF. Impact of ERBB2 mutations on in vitro sensitivity of bladder cancer to lapatinib. Cancer Biol Ther 2014; 15:1239-47.
    • 4 Nagano M, Kohsaka S, Ueno T, Kojima S, Saka K, Iwase H, Kawazu M, Mano H. High-Throughput Functional Evaluation of Variants of Unknown Significance in ERBB2. Clin Cancer Res 2018; 24:5112-5122.
    • 4 Pahuja KB, Nguyen TT, Jaiswal BS, Prabhash K, Thaker TM, Senger K, Chaudhuri S, Kljavin NM, Antony A, Phalke S, Kumar P, Mravic M, Stawiski EW, Vargas D, Durinck S, Gupta R, Khanna-Gupta A, Trabucco SE, Sokol ES, Hartmaier RJ, Singh A, Chougule A, Trivedi V, Dutt A, Patil V, Joshi A, Noronha V, Ziai J, Banavali SD, Ramprasad V, DeGrado WF, Bueno R, Jura N, Seshagiri S. Actionable Activating Oncogenic ERBB2/HER2 Transmembrane and Juxtamembrane Domain Mutations. Cancer Cell 2018; 34:792-806.e5.
    • 4 Robichaux JP, Elamin YY, Vijayan RSK, Nilsson MB, Hu L, He J, Zhang F, Pisegna M, Poteete A, Sun H, Li S, Chen T, Han H, Negrao MV, Ahnert JR, Diao L, Wang J, Le X, Meric-Bernstam F, Routbort M, Roeck B, Yang Z, Raymond VM, Lanman RB, Frampton GM, Miller VA, Schrock AB, Albacker LA, Wong KK, Cross JB, Heymach JV. Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 Activity. Cancer Cell 2019; 36:444-457.e7.
    • 4 Gaibar M, Beltrán L, Romero-Lorca A, Fernández-Santander A, Novillo A. Somatic Mutations in HER2 and Implications for Current Treatment Paradigms in HER2-Positive Breast Cancer. J Oncol 2020; 2020:6375956. eCollection 2020.
    • Lapatinib + Afatinib
    • ERBB4
    • 4 Goss GD, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Li W, Guclu S, Isla D, Min YJ, Morabito A, Ardizzoni A, Gadgeel SM, Fülöp A, Bühnemann C, Gibson N, Krämer N, Solca F, Cseh A, Ehrnrooth E, Soria JC. Association of ERBB Mutations With Clinical Outcomes of Afatinib- or Erlotinib-Treated Patients With Lung Squamous Cell Carcinoma: Secondary Analysis of the LUX-Lung 8 Randomized Clinical Trial. JAMA Oncol 2018; 4:1189-1197.
    • Lapatinib + Capecitabine
    • ERBB2
    • R2 Xu X, De Angelis C, Burke KA, Nardone A, Hu H, Qin L, Veeraraghavan J, Sethunath V, Heiser LM, Wang N, Ng CKY, Chen ES, Renwick A, Wang T, Nanda S, Shea M, Mitchell T, Rajendran M, Waters I, Zabransky DJ, Scott KL, Gutierrez C, Nagi C, Geyer FC, Chamness GC, Park BH, Shaw CA, Hilsenbeck SG, Rimawi MF, Gray JW, Weigelt B, Reis-Filho JS, Osborne CK, Schiff R. HER2 Reactivation through Acquisition of the HER2 L755S Mutation as a Mechanism of Acquired Resistance to HER2-targeted Therapy in HER2+ Breast Cancer. Clin Cancer Res 2017; 23:5123-5134.
    • ERBB2
    • 1 Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006; 355:2733-43.
    • ERBB2
    • 4 Vornicova O, Hershkovitz D, Yablonski-Peretz T, Ben-Itzhak O, Keidar Z, Bar-Sela G. Treatment of metastatic extramammary Paget's disease associated with adnexal adenocarcinoma, with anti-HER2 drugs based on genomic alteration ERBB2 S310F. Oncologist 2014; 19:1006-7.
    • Lapatinib + Letrozole
    • ERBB2
    • 1B Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol 2009; 27:5538-46.
    • ERBB2
    • R2 Xu X, De Angelis C, Burke KA, Nardone A, Hu H, Qin L, Veeraraghavan J, Sethunath V, Heiser LM, Wang N, Ng CKY, Chen ES, Renwick A, Wang T, Nanda S, Shea M, Mitchell T, Rajendran M, Waters I, Zabransky DJ, Scott KL, Gutierrez C, Nagi C, Geyer FC, Chamness GC, Park BH, Shaw CA, Hilsenbeck SG, Rimawi MF, Gray JW, Weigelt B, Reis-Filho JS, Osborne CK, Schiff R. HER2 Reactivation through Acquisition of the HER2 L755S Mutation as a Mechanism of Acquired Resistance to HER2-targeted Therapy in HER2+ Breast Cancer. Clin Cancer Res 2017; 23:5123-5134.
    • Lapatinib + Paclitaxel
    • ERBB2
    • 1B Guan Z, Xu B, DeSilvio ML, Shen Z, Arpornwirat W, Tong Z, Lorvidhaya V, Jiang Z, Yang J, Makhson A, Leung WL, Russo MW, Newstat B, Wang L, Chen G, Oliva C, Gomez H. Randomized trial of lapatinib versus placebo added to paclitaxel in the treatment of human epidermal growth factor receptor 2-overexpressing metastatic breast cancer. J Clin Oncol 2013; 31:1947-53.
    • ERBB2
    • R2 Xu X, De Angelis C, Burke KA, Nardone A, Hu H, Qin L, Veeraraghavan J, Sethunath V, Heiser LM, Wang N, Ng CKY, Chen ES, Renwick A, Wang T, Nanda S, Shea M, Mitchell T, Rajendran M, Waters I, Zabransky DJ, Scott KL, Gutierrez C, Nagi C, Geyer FC, Chamness GC, Park BH, Shaw CA, Hilsenbeck SG, Rimawi MF, Gray JW, Weigelt B, Reis-Filho JS, Osborne CK, Schiff R. HER2 Reactivation through Acquisition of the HER2 L755S Mutation as a Mechanism of Acquired Resistance to HER2-targeted Therapy in HER2+ Breast Cancer. Clin Cancer Res 2017; 23:5123-5134.
    • Lapatinib + Trastuzumab
    • BRAF, KRAS
    • R2 Sartore-Bianchi A, Trusolino L, Martino C, Bencardino K, Lonardi S, Bergamo F, Zagonel V, Leone F, Depetris I, Martinelli E, Troiani T, Ciardiello F, Racca P, Bertotti A, Siravegna G, Torri V, Amatu A, Ghezzi S, Marrapese G, Palmeri L, Valtorta E, Cassingena A, Lauricella C, Vanzulli A, Regge D, Veronese S, Comoglio PM, Bardelli A, Marsoni S, Siena S. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol 2016; 17:738-746.
    • ERBB2
    • R2 Xu X, De Angelis C, Burke KA, Nardone A, Hu H, Qin L, Veeraraghavan J, Sethunath V, Heiser LM, Wang N, Ng CKY, Chen ES, Renwick A, Wang T, Nanda S, Shea M, Mitchell T, Rajendran M, Waters I, Zabransky DJ, Scott KL, Gutierrez C, Nagi C, Geyer FC, Chamness GC, Park BH, Shaw CA, Hilsenbeck SG, Rimawi MF, Gray JW, Weigelt B, Reis-Filho JS, Osborne CK, Schiff R. HER2 Reactivation through Acquisition of the HER2 L755S Mutation as a Mechanism of Acquired Resistance to HER2-targeted Therapy in HER2+ Breast Cancer. Clin Cancer Res 2017; 23:5123-5134.
    • ERBB2
    • 2 Blackwell KL, Burstein HJ, Storniolo AM, Rugo H, Sledge G, Koehler M, Ellis C, Casey M, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J. Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol 2010; 28:1124-30.
    • ERBB2
    • 3 Sartore-Bianchi A, Trusolino L, Martino C, Bencardino K, Lonardi S, Bergamo F, Zagonel V, Leone F, Depetris I, Martinelli E, Troiani T, Ciardiello F, Racca P, Bertotti A, Siravegna G, Torri V, Amatu A, Ghezzi S, Marrapese G, Palmeri L, Valtorta E, Cassingena A, Lauricella C, Vanzulli A, Regge D, Veronese S, Comoglio PM, Bardelli A, Marsoni S, Siena S. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol 2016; 17:738-746.
    • ERBB2
    • 4 Bose R, Kavuri SM, Searleman AC, Shen W, Shen D, Koboldt DC, Monsey J, Goel N, Aronson AB, Li S, Ma CX, Ding L, Mardis ER, Ellis MJ. Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer Discov 2013; 3:224-37.
    • ERBB3
    • 4 Bidard FC, Ng CK, Cottu P, Piscuoglio S, Escalup L, Sakr RA, Reyal F, Mariani P, Lim R, Wang L, Norton L, Servois V, Sigal B, Vincent-Salomon A, Weigelt B, Pierga JY, Reis-Filho JS. Response to dual HER2 blockade in a patient with HER3-mutant metastatic breast cancer. Ann Oncol 2015; 26:1704-9.
    • Larotrectinib
    • NTRK2
    • R1 Adriana Estrada-Bernal, Anh T. Le, Brian Tuch, Tatiana G. Kutateladze, Robert C. Doebele. Identification of TRKA and TRKB kinase domain mutations that induce resistance to a pan-TRK inhibitor. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-118.
    • NTRK1, NTRK3
    • R1 Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 2018; 15:731-747.
    • NTRK1, NTRK2, NTRK3
    • R2 David S. Hong, Afshin Dowlati, Howard Burris, Edward Chu, Marcia S. Brose, Anna F. Farago, Cornelis M. van Tilburg, Shivaani Kummar, Leo Mascarenhas, John A. Reeves, Marion Rudolph, Patricia Maeda, Barrett H. Childs, Theodore W. Laetsch, Alexander Drilon. Efficacy and safety of larotrectinib in patients with cancer and NTRK gene fusions or other alterations [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT062.
    • NTRK1, NTRK2, NTRK3
    • 1 Tilburg CMv, DuBois SG, Albert CM, Federman N, Nagasubramanian R, Geoerger B, Orbach D, Bielack SS, Shukla NN, Turpin B, Casanova M, Spunt SL, Qamoos H, Nanda S, Childs BH, Cox MC, Pappo AS, Laetsch TW, Mascarenhas L. Larotrectinib efficacy and safety in pediatric TRK fusion cancer patients. J Clin Oncol 2019; 37(15_suppl): 10010-10010.
    • 1 Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD, Nathenson M, Doebele RC, Farago AF, Pappo AS, Turpin B, Dowlati A, Brose MS, Mascarenhas L, Federman N, Berlin J, El-Deiry WS, Baik C, Deeken J, Boni V, Nagasubramanian R, Taylor M, Rudzinski ER, Meric-Bernstam F, Sohal DPS, Ma PC, Raez LE, Hechtman JF, Benayed R, Ladanyi M, Tuch BB, Ebata K, Cruickshank S, Ku NC, Cox MC, Hawkins DS, Hong DS, Hyman DM. Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med 2018; 378:731-739.
    • 1 Hong DS, DuBois SG, Kummar S, Farago AF, Albert CM, Rohrberg KS, van Tilburg CM, Nagasubramanian R, Berlin JD, Federman N, Mascarenhas L, Geoerger B, Dowlati A, Pappo AS, Bielack S, Doz F, McDermott R, Patel JD, Schilder RJ, Tahara M, Pfister SM, Witt O, Ladanyi M, Rudzinski ER, Nanda S, Childs BH, Laetsch TW, Hyman DM, Drilon A. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol 2020; 21:531-540.
    • NTRK1, NTRK2, NTRK3
    • 3 . . [DOI:]
    • NTRK2
    • 4 Mangum R, Reuther J, Bertrand KC, Chandramohan R, Kukreja MK, Paulino AC, Muzny D, Hu J, Gibbs RA, Curry DJ, Malbari F, Chintagumpala MM, Adesina AM, Fisher KE, Mack SC, Plon SE, Roy A, Parsons DW, Lin FY. Durable Response to Larotrectinib in a Child With Histologic Diagnosis of Recurrent Disseminated Ependymoma Discovered to Harbor an NTRK2 Fusion: The Impact of Integrated Genomic Profiling. JCO Prec Oncol 2020; 10.1200/PO.20.00375 5 1221-1227. Published online July 28, 2021.
    • NTRK1, NTRK2, NTRK3
    • NTRK1
    • 4 Hempel D, Wieland T, Solfrank B, Grossmann V, Steinhard J, Frick A, Hempel L, Eberl T, Gaumann A. Antitumor Activity of Larotrectinib in Esophageal Carcinoma with NTRK Gene Amplification. Oncologist 2020; 25:e881-e886.
    • Lasofoxifene + Abemaciclib
    • ESR1
    • 4 Damodaran S, Plourde PV, Moore HCF, Anderson IC, Portman DJ. Open-label, phase 2, multicenter study of lasofoxifene (LAS) combined with abemaciclib (Abema) for treating pre- and postmenopausal women with locally advanced or metastatic ER+/HER2− breast cancer and an ESR1 mutation after progression on prior therapies. J Clin Oncol 2022; 40(16_suppl): 1022-1022.
    • Lazertinib
    • EGFR
    • R2 Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 2021; 597:732-737.
    • EGFR
    • 4 Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 2021; 597:732-737.
    • Lazertinib
    • EGFR
    • R2 Lee C, Kim M, Kim DW, Kim TM, Kim S, Im SW, Jeon YK, Keam B, Ku JL, Heo DS. Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non-Small Cell Lung Cancer. Cancer Res Treat 2021 May 3. [Epub ahead of print]
    • EGFR
    • 4 Lee C, Kim M, Kim DW, Kim TM, Kim S, Im SW, Jeon YK, Keam B, Ku JL, Heo DS. Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non-Small Cell Lung Cancer. Cancer Res Treat 2021 May 3. [Epub ahead of print]
    • Lenalidomide + Rituximab
    • CD20
    • 2 Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma. N Engl J Med 2018; 379:934-947.
    • 2 Becnel MR, Nastoupil LJ, Samaniego F, Davis RE, You MJ, Green M, Hagemeister FB, Fanale MA, Fayad LE, Westin JR, Wang M, Oki Y, Forbes SG, Feng L, Neelapu SS, Fowler NH. Lenalidomide plus rituximab (R2 ) in previously untreated marginal zone lymphoma: subgroup analysis and long-term follow-up of an open-label phase 2 trial. Br J Haematol 2019; 185:874-882.
    • Lenvatinib
    • RET
    • 3 Hida T, Velcheti V, Reckamp KL, Nokihara H, Sachdev P, Kubota T, Nakada T, Dutcus CE, Ren M, Tamura T. A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma. Lung Cancer 2019; 138:124-130.
    • SSTR2
    • 3 Capdevila J, Fazio N, Lopez C, Teulé A, Valle JW, Tafuto S, Custodio A, Reed N, Raderer M, Grande E, Garcia-Carbonero R, Jimenez-Fonseca P, Hernando J, Bongiovanni A, Spada F, Alonso V, Antonuzzo L, Spallanzani A, Berruti A, La Casta A, Sevilla I, Kump P, Giuffrida D, Merino X, Trejo L, Gajate P, Matos I, Lamarca A, Ibrahim T. Lenvatinib in Patients With Advanced Grade 1/2 Pancreatic and Gastrointestinal Neuroendocrine Tumors: Results of the Phase II TALENT Trial (GETNE1509). J Clin Oncol 2021 May 4:JCO2003368. [Epub ahead of print]
    • RET
    • 4 Subbiah V, Yang D, Velcheti V, Drilon A, Meric-Bernstam F. State-of-the-Art Strategies for Targeting RET-Dependent Cancers. J Clin Oncol 2020; 38:1209-1221.
    • Lenvatinib + Pembrolizumab
    • Microsatellite instability+Mismatch repair
    • 1B Makker V, Rasco D, Vogelzang NJ, Brose MS, Cohn AL, Mier J, Di Simone C, Hyman DM, Stepan DE, Dutcus CE, Schmidt EV, Guo M, Sachdev P, Shumaker R, Aghajanian C, Taylor M. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol 2019; 20:711-718.
    • 1B Makker V, Taylor MH, Aghajanian C, Oaknin A, Mier J, Cohn AL, Romeo M, Bratos R, Brose MS, DiSimone C, Messing M, Stepan DE, Dutcus CE, Wu J, Schmidt EV, Orlowski R, Sachdev P, Shumaker R, Casado Herraez A. Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer. J Clin Oncol 2020; 38:2981-2992.
    • Letrozole
    • ESR1
    • R2 Jeselsohn R, Buchwalter G, De Angelis C, Brown M, Schiff R. ESR1 mutations—a mechanism for acquired endocrine resistance in breast cancer. Nat Rev Clin Oncol 2015; 12:573-83.
    • PGR
    • 1 McGuire WL, Horwitz KB, Pearson OH, Segaloff A. Current status of estrogen and progesterone receptors in breast cancer. Cancer 1977; 39(6 Suppl):2934-47.
    • 1 Kiang DT, Kennedy BJ. Tamoxifen (antiestrogen) therapy in advanced breast cancer. Ann Intern Med 1977; 87:687-90.
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    • 1 Stuart NS, Warwick J, Blackledge GR, Spooner D, Keen C, Taylor AR, Tyrell C, Webster DJ, Earl H. A randomised phase III cross-over study of tamoxifen versus megestrol acetate in advanced and recurrent breast cancer. Eur J Cancer 1996; 32A:1888-92.
    • 1 Taylor CW, Green S, Dalton WS, Martino S, Rector D, Ingle JN, Robert NJ, Budd GT, Paradelo JC, Natale RB, Bearden JD, Mailliard JA, Osborne CK. Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer: an intergroup study. J Clin Oncol 1998; 16:994-9.
    • 1 The Exemestane Study Group. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial.. J Clin Oncol 2000; 18:1399-411.
    • ESR1, PGR
    • 1 Mouridsen H, Gershanovich M, Sun Y, Pérez-Carrión R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Jänicke F, Pluzanska A, Dank M, Becquart D, Bapsy PP, Salminen E, Snyder R, Lassus M, Verbeek JA, Staffler B, Chaudri-Ross HA, Dugan M. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 2001; 19:2596-606.
    • PGR
    • 1 Bonneterre J, Buzdar A, Nabholtz JM, Robertson JF, Thürlimann B, von Euler M, Sahmoud T, Webster A, Steinberg M; Arimidex Writing Committee; Investigators Committee Members. Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma. Cancer 2001; 92:2247-58.
    • ESR1
    • 4 van Weelden WJ, Massuger LFAG; ENITEC, Pijnenborg JMA, Romano A. Anti-estrogen Treatment in Endometrial Cancer: A Systematic Review. Front Oncol 2019; 9:359. eCollection 2019.
    • Lifirafenib
    • BRAF, KRAS
    • 4 Desai J, Gan H, Barrow C, Jameson M, Atkinson V, Haydon A, Millward M, Begbie S, Brown M, Markman B, Patterson W, Hill A, Horvath L, Nagrial A, Richardson G, Jackson C, Friedlander M, Parente P, Tran B, Wang L, Chen Y, Tang Z, Huang W, Wu J, Zeng D, Luo L, Solomon B. Phase I, Open-Label, Dose-Escalation/Dose-Expansion Study of Lifirafenib (BGB-283), an RAF Family Kinase Inhibitor, in Patients With Solid Tumors. J Clin Oncol 2020; 38:2140-2150.
    • Linsitinib + Erlotinib
    • EGFR
    • R2 Leighl NB, Rizvi NA, de Lima LG Jr, Arpornwirat W, Rudin CM, Chiappori AA, Ahn MJ, Chow LQ, Bazhenova L, Dechaphunkul A, Sunpaweravong P, Eaton K, Chen J, Medley S, Poondru S, Singh M, Steinberg J, Juergens RA, Gadgeel SM. Phase 2 Study of Erlotinib in Combination With Linsitinib (OSI-906) or Placebo in Chemotherapy-Naive Patients With Non-Small-Cell Lung Cancer and Activating Epidermal Growth Factor Receptor Mutations. Clin Lung Cancer 2017; 18:34-42.e2.
    • Lorlatinib
    • ALK
    • R2 J. Jean Cui, Evan Rogers, Dayong Zhai, Wei Deng, Jane Ung, Vivian Nguyen, Han Zhang, Xin Zhang, Ana Parra, Maria Barrera, Dong Lee, Brion Murray. TPX-0131: A next generation macrocyclic ALK inhibitor that overcomes ALK resistant mutations refractory to current approved ALK inhibitors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5226.
    • ROS1
    • R2 Davare MA, Vellore NA, Wagner JP, Eide CA, Goodman JR, Drilon A, Deininger MW, O'Hare T, Druker BJ. Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors. Proc Natl Acad Sci U S A 2015; 112:E5381-90.
    • ALK
    • R2 Lin JJ, Riely GJ, Shaw AT. Targeting ALK: Precision Medicine Takes on Drug Resistance. Cancer Discov 2017; 7:137-155.
    • ROS1
    • R2 Guisier F, Piton N, Salaun M, Thiberville L. ROS1-rearranged NSCLC With Secondary Resistance Mutation: Case Report and Current Perspectives. Clin Lung Cancer 2019; 20:e593-e596.
    • ALK
    • 1 Solomon B, Bauer T, Marinis FD, Felip E, Goto Y, Liu G, Mazieres J, Kim D, Mok T, Polli A, Thurm H, Calella A, Peltz G, Shaw A. LBA2 Lorlatinib vs crizotinib in the first-line treatment of patients (pts) with advanced ALK-positive non-small cell lung cancer (NSCLC): Results of the phase III CROWN study. Ann Oncol 2020; 31 (4): S1180. 10.1016/j.annonc.2020.08.2282
    • 1 Solomon BJ, Besse B, Bauer TM, Felip E, Soo RA, Camidge DR, Chiari R, Bearz A, Lin CC, Gadgeel SM, Riely GJ, Tan EH, Seto T, James LP, Clancy JS, Abbattista A, Martini JF, Chen J, Peltz G, Thurm H, Ou SI, Shaw AT. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol 2018; 19:1654-1667.
    • 1 Shaw AT, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, Mazieres J, Kim DW, Mok T, Polli A, Thurm H, Calella AM, Peltz G, Solomon BJ; CROWN Trial Investigators. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. N Engl J Med 2020; 383:2018-2029.
    • ROS1
    • 2 Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, Gainor JF, Johnson M, Dietrich J, James LP, Clancy JS, Chen J, Martini JF, Abbattista A, Solomon BJ. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol 2017; 18:1590-1599.
    • 2 Shaw AT, Solomon BJ, Chiari R, Riely GJ, Besse B, Soo RA, Kao S, Lin CC, Bauer TM, Clancy JS, Thurm H, Martini JF, Peltz G, Abbattista A, Li S, Ou SI. Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 1-2 trial. Lancet Oncol 2019; 20:1691-1701.
    • ALK
    • 3 Lin JJ, Riely GJ, Shaw AT. Targeting ALK: Precision Medicine Takes on Drug Resistance. Cancer Discov 2017; 7:137-155.
    • 3 Shaw AT, Solomon BJ, Besse B, Bauer TM, Lin CC, Soo RA, Riely GJ, Ou SI, Clancy JS, Li S, Abbattista A, Thurm H, Satouchi M, Camidge DR, Kao S, Chiari R, Gadgeel SM, Felip E, Martini JF. ALK Resistance Mutations and Efficacy of Lorlatinib in Advanced Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer. J Clin Oncol 2019; 37:1370-1379.
    • ALK
    • 4 Goldsmith KC, Kayser K, Groshen SG, Chioda M, Thurm HC, Chen J, Peltz G, Granger M, Maris J, Matthay KK, Ghazarian S, Park JR, Berko E, Marachelian A, Mosse YP. Phase I trial of lorlatinib in patients with ALK-driven refractory or relapsed neuroblastoma: A New Approaches to Neuroblastoma Consortium study. J Clin Oncol 2020; 38(15_suppl): 10504-10504.
    • 4 Bagchi A, Orr BA, Campagne O, Dhanda S, Nair S, Tran Q, Christensen AM, Gajjar A, Furtado LV, Vasilyeva A, Boop F, Stewart C, Robinson GW. Lorlatinib in a Child with ALK-Fusion-Positive High-Grade Glioma. N Engl J Med 2021; 385:761-763.
    • Lu-177 vipivotide tetraxetan
    • PSMA
    • 2 Morris MJ, Bono JSD, Chi KN, Fizazi K, Herrmann K, Rahbar K, Tagawa ST, Nordquist LT, Vaishampayan N, El-Haddad G, Park CH, Beer TM, Pérez-Contreras WJ, Desilvio M, Kpamegan EE, Gericke G, Messmann RA, Krause BJ, Sartor AO. Phase III study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION). J Clin Oncol 2021; 39(18_suppl):
    • 2 Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, Tagawa ST, Nordquist LT, Vaishampayan N, El-Haddad G, Park CH, Beer TM, Armour A, Pérez-Contreras WJ, DeSilvio M, Kpamegan E, Gericke G, Messmann RA, Morris MJ, Krause BJ; VISION Investigators. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2021 Jun 23. [Epub ahead of print]
    • PSMA
    • 3 Hofman MS, Emmett L, Sandhu SK, Iravani A, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Zhang AY, McJannett MM, Stockler MR, Violet JA, Williams S, Martin AJ, Davis ID. TheraP: A randomised phase II trial of ^177Lu-PSMA-617 (LuPSMA) theranostic versus cabazitaxel in metastatic castration resistant prostate cancer (mCRPC) progressing after docetaxel: Initial results (ANZUP protocol 1603). J Clin Oncol 2020; 38(15_suppl): 5500-5500.
    • 3 Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, Iravani A, Kong G, Ravi Kumar A, Murphy DG, Eu P, Jackson P, Scalzo M, Williams SG, Sandhu S. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol 2018; 19:825-833.
    • Lucitanib
    • FGFR1
    • 3 Hui R, Pearson A, Cortes J, Campbell C, Poirot C, Azim HA Jr, Fumagalli D, Lambertini M, Daly F, Arahmani A, Perez-Garcia J, Aftimos P, Bedard PL, Xuereb L, Scheepers ED, Vicente M, Goulioti T, Loibl S, Loi S, Pierrat MJ, Turner NC, Andre F, Curigliano G. Lucitanib for the Treatment of HR+/HER2- Metastatic Breast Cancer: Results from the Multicohort Phase II FINESSE Study. Clin Cancer Res 2020; 26:354-363.
    • Lumretuzumab
    • NRG1
    • 4 Cejalvo JM, Jacob W, Fleitas Kanonnikoff T, Felip E, Navarro Mendivil A, Martinez Garcia M, Taus Garcia A, Leighl N, Lassen U, Mau-Soerensen M, Adessi C, Michielin F, James I, Ceppi M, Hasmann M, Weisser M, Cervantes A. A phase Ib/II study of HER3-targeting lumretuzumab in combination with carboplatin and paclitaxel as first-line treatment in patients with advanced or metastatic squamous non-small cell lung cancer. ESMO Open 2019; 4:e000532. eCollection 2019.
    • Lumretuzumab + Erlotinib
    • NRG1
    • 4 Kim HS, Han JY, Shin DH, Lim KY, Lee GK, Kim JY, Jacob W, Ceppi M, Weisser M, James I. EGFR and HER3 signaling blockade in invasive mucinous lung adenocarcinoma harboring an NRG1 fusion. Lung Cancer 2018; 124:71-75.
    • M
    • M6620
    • ARID1A
    • 4 Williamson CT, Miller R, Pemberton HN, Jones SE, Campbell J, Konde A, Badham N, Rafiq R, Brough R, Gulati A, Ryan CJ, Francis J, Vermulen PB, Reynolds AR, Reaper PM, Pollard JR, Ashworth A, Lord CJ. ATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1A. Nat Commun 2016; 7:13837.
    • 4 Yap TA, O'Carrigan B, Penney MS, Lim JS, Brown JS, de Miguel Luken MJ, Tunariu N, Perez-Lopez R, Rodrigues DN, Riisnaes R, Figueiredo I, Carreira S, Hare B, McDermott K, Khalique S, Williamson CT, Natrajan R, Pettitt SJ, Lord CJ, Banerji U, Pollard J, Lopez J, de Bono JS. Phase I Trial of First-in-Class ATR Inhibitor M6620 (VX-970) as Monotherapy or in Combination With Carboplatin in Patients With Advanced Solid Tumors. J Clin Oncol 2020; 38:3195-3204.
    • MDM2 inhibitor
    • TP53
    • R2 Jung J, Lee JS, Dickson MA, Schwartz GK, Le Cesne A, Varga A, Bahleda R, Wagner AJ, Choy E, de Jonge MJ, Light M, Rowley S, Macé S, Watters J. TP53 mutations emerge with HDM2 inhibitor SAR405838 treatment in de-differentiated liposarcoma. Nat Commun 2016; 7:12609.
    • R2 Sanz G, Singh M, Peuget S, Selivanova G. Inhibition of p53 inhibitors: progress, challenges and perspectives. J Mol Cell Biol 2019; 11:586-599.
    • MEDI7247
    • SLC1A5
    • 4 Kevin P. Schifferli, Noel R. Monks, Ravinder Tammali, M Jack Borrok, Matthew G. Flynn, Elaine M. Hurt, Steven R. Coats, Ronald Herbst, David A. Tice, Nabendu Pore. MEDI7247: A first in class antibody drug conjugate targeting ASCT2 in a range of solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-298.
    • 4 Fathi AT, Donnellan WB, Lyons RM, Maris MB, Kim TM, Kim WS, Schiller GJ, Abboud CN, Arellano ML, Cull EH, Yee KWL, Townsley DM, Wang F, Bothos JG, Yao N, Salles GA. A phase 1 multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity of MEDI7247 in patients with select relapsed/refractory hematologic malignancies. J Clin Oncol 2018; 36(15_suppl):
    • MEK inhibitor
    • KRAS
    • R2 Sun C, Hobor S, Bertotti A, Zecchin D, Huang S, Galimi F, Cottino F, Prahallad A, Grernrum W, Tzani A, Schlicker A, Wessels LF, Smit EF, Thunnissen E, Halonen P, Lieftink C, Beijersbergen RL, Di Nicolantonio F, Bardelli A, Trusolino L, Bernards R. Intrinsic resistance to MEK inhibition in KRAS mutant lung and colon cancer through transcriptional induction of ERBB3. Cell Rep 2014; 7:86-93.
    • R2 Lito P, Saborowski A, Yue J, Solomon M, Joseph E, Gadal S, Saborowski M, Kastenhuber E, Fellmann C, Ohara K, Morikami K, Miura T, Lukacs C, Ishii N, Lowe S, Rosen N. Disruption of CRAF-mediated MEK activation is required for effective MEK inhibition in KRAS mutant tumors. Cancer Cell 2014; 25:697-710.
    • R2 Samatar AA, Poulikakos PI. Targeting RAS-ERK signalling in cancer: promises and challenges. Nat Rev Drug Discov 2014; 13:928-42.
    • HGF
    • R2 Ahn SY, Kim J, Kim MA, Choi J, Kim WH. Increased HGF Expression Induces Resistance to c-MET Tyrosine Kinase Inhibitors in Gastric Cancer. Anticancer Res 2017; 37:1127-1138.
    • MAP2K1
    • 4 Smalley I, Smalley KSM. ERK Inhibition: A New Front in the War against MAPK Pathway-Driven Cancers? Cancer Discov 2018; 8:140-142.
    • BRAF
    • 4 Yaeger R, Corcoran RB. Targeting Alterations in the RAF-MEK Pathway. Cancer Discov 2019; 9:329-341.
    • MEK inhibitor + SHP2 inhibitor
    • KRAS
    • 4 Ruess DA, Heynen GJ, Ciecielski KJ, Ai J, Berninger A, Kabacaoglu D, Görgülü K, Dantes Z, Wörmann SM, Diakopoulos KN, Karpathaki AF, Kowalska M, Kaya-Aksoy E, Song L, van der Laan EAZ, López-Alberca MP, Nazaré M, Reichert M, Saur D, Erkan MM, Hopt UT, Sainz B Jr, Birchmeier W, Schmid RM, Lesina M, Algül H. Mutant KRAS-driven cancers depend on PTPN11/SHP2 phosphatase. Nat Med 2018; 24:954-960.
    • 4 Fedele C, Ran H, Diskin B, Wei W, Jen J, Geer MJ, Araki K, Ozerdem U, Simeone DM, Miller G, Neel BG, Tang KH. SHP2 Inhibition Prevents Adaptive Resistance to MEK Inhibitors in Multiple Cancer Models. Cancer Discov 2018; 8:1237-1249.
    • 4 Lu H, Liu C, Velazquez R, Wang H, Dunkl LM, Kazic-Legueux M, Haberkorn A, Billy E, Manchado E, Brachmann SM, Moody SE, Engelman JA, Hammerman PS, Caponigro G, Mohseni M, Hao HX. SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors. Mol Cancer Ther 2019; 18:1323-1334.
    • 4 Hao HX, Wang H, Liu C, Kovats S, Velazquez R, Lu H, Pant B, Shirley M, Meyer MJ, Pu M, Lim J, Fleming M, Alexander L, Farsidjani A, LaMarche MJ, Moody S, Silver SJ, Caponigro G, Stuart DD, Abrams TJ, Hammerman PS, Williams J, Engelman JA, Goldoni S, Mohseni M. Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers. Mol Cancer Ther 2019; 18:2368-2380.
    • MEK inhibitor + anti-EGFR monoclonal antibody
    • BRAF
    • 4 Dankner M. Targeted Therapy for Colorectal Cancers With Non-V600 BRAF Mutations: Perspectives for Precision Oncology. JCO Prec Oncol 2018; - published online November 8, 2018
    • 4 Yao Z, Yaeger R, Rodrik-Outmezguine VS, Tao A, Torres NM, Chang MT, Drosten M, Zhao H, Cecchi F, Hembrough T, Michels J, Baumert H, Miles L, Campbell NM, de Stanchina E, Solit DB, Barbacid M, Taylor BS, Rosen N. Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS. Nature 2017; 548:234-238.
    • MGC018
    • CD276
    • 4 Shenderov E, Mallesara G, Wysocki P, Xu W, Ramlau R, Weickhardt A, Zolnierek J, Spira A, Joshua A, Powderly J, Antonarakis E, Jang S, Aragon-Ching J, Shen J, Paller C, Vogelzang N, Leu K, Cortés J, Bohac C, Lugowska I. 620P MGC018, an anti-B7-H3 antibody-drug conjugate (ADC), in patients with advanced solid tumors: Preliminary results of phase I cohort expansion. Ann Oncol 2021; 32 (5): S657. 10.1016/j.annonc.2021.08.1133
    • 4 Jang S, Powderly JD, Spira AI, Bakkacha O, Loo D, Bohac GC, Sharma M. Phase 1 dose escalation study of MGC018, an anti-B7-H3 antibody-drug conjugate (ADC), in patients with advanced solid tumors. J Clin Oncol 2021; 39(15_suppl): 2631-2631.
    • MIL93
    • CLDN18
    • 4 . . [DOI:]
    • MK-2206 + Gemcitabine
    • EGFR+ERRFI1
    • 4 Cairns J, Fridley BL, Jenkins GD, Zhuang Y, Yu J, Wang L. Differential roles of ERRFI1 in EGFR and AKT pathway regulation affect cancer proliferation. EMBO Rep 2018; 19(3). pii: e44767.
    • MK2206
    • PIK3CA, PTEN
    • R2 Dasari A, Overman MJ, Fogelman DR, Kee BK, Menter D, Raghav KPS, Morris VK, Oh J, Wu J, Jiang Z, Tian F, Adam L, Brimer M, Morris J, Meric-Bernstam F, Kopetz S. A phase II and co-clinical study of an AKT inhibitor in patients (pts) with biomarker-enriched, previously treated metastatic colorectal cancer (mCRC). J Clin Oncol 2016; 34(15_suppl): 3563-3563.
    • MORAb-202
    • FOLR1
    • 4 . . [DOI:]
    • 4 Shimizu T, Fujiwara Y, Yonemori K, Koyama T, Sato J, Tamura K, Shimomura A, Ikezawa H, Nomoto M, Furuuchi K, Nakajima R, Miura T, Yamamoto N. First-in-Human Phase 1 Study of MORAb-202, an Antibody-Drug Conjugate Comprising Farletuzumab Linked to Eribulin Mesylate, in Patients with Folate Receptor-α-Positive Advanced Solid Tumors. Clin Cancer Res 2021; 27:3905-3915.
    • MRK003
    • NOTCH3
    • 4 Konishi J, Kawaguchi KS, Vo H, Haruki N, Gonzalez A, Carbone DP, Dang TP. Gamma-secretase inhibitor prevents Notch3 activation and reduces proliferation in human lung cancers. Cancer Res 2007; 67:8051-7.
    • NOTCH2
    • 4 Fan X, Khaki L, Zhu TS, Soules ME, Talsma CE, Gul N, Koh C, Zhang J, Li YM, Maciaczyk J, Nikkhah G, Dimeco F, Piccirillo S, Vescovi AL, Eberhart CG. NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts. Stem Cells 2010; 28:5-16.
    • NOTCH1
    • 4 Groeneweg JW, Hall TR, Zhang L, Kim M, Byron VF, Tambouret R, Sathayanrayanan S, Foster R, Rueda BR, Growdon WB. Inhibition of gamma-secretase activity impedes uterine serous carcinoma growth in a human xenograft model. Gynecol Oncol 2014; 133:607-15.
    • 4 Stoeck A, Lejnine S, Truong A, Pan L, Wang H, Zang C, Yuan J, Ware C, MacLean J, Garrett-Engele PW, Kluk M, Laskey J, Haines BB, Moskaluk C, Zawel L, Fawell S, Gilliland G, Zhang T, Kremer BE, Knoechel B, Bernstein BE, Pear WS, Liu XS, Aster JC, Sathyanarayanan S. Discovery of biomarkers predictive of GSI response in triple-negative breast cancer and adenoid cystic carcinoma. Cancer Discov 2014; 4:1154-67.
    • MRK003 + paclitaxel
    • NOTCH2
    • 4 Stoeck A, Lejnine S, Truong A, Pan L, Wang H, Zang C, Yuan J, Ware C, MacLean J, Garrett-Engele PW, Kluk M, Laskey J, Haines BB, Moskaluk C, Zawel L, Fawell S, Gilliland G, Zhang T, Kremer BE, Knoechel B, Bernstein BE, Pear WS, Liu XS, Aster JC, Sathyanarayanan S. Discovery of biomarkers predictive of GSI response in triple-negative breast cancer and adenoid cystic carcinoma. Cancer Discov 2014; 4:1154-67.
    • MRTX1133
    • KRAS
    • 4 Wang X, Allen S, Blake JF, Bowcut V, Briere DM, Calinisan A, Dahlke JR, Fell JB, Fischer JP, Gunn RJ, Hallin J, Laguer J, Lawson JD, Medwid J, Newhouse B, Nguyen P, O'Leary JM, Olson P, Pajk S, Rahbaek L, Rodriguez M, Smith CR, Tang TP, Thomas NC, Vanderpool D, Vigers GP, Christensen JG, Marx MA. Identification of MRTX1133, a Noncovalent, Potent, and Selective KRASG12D Inhibitor. J Med Chem 2021 Dec 10. [Epub ahead of print]
    • MT-5111
    • ERBB2
    • 4 Jack P Higgins, Asis Sarkar, Eric T Williams, Aimee Iberg, Roger Waltzman, Erin K Willert. MT-5111, a novel HER2 targeting engineered toxin body, under clinical development to overcome mechanisms of resistance to existing HER2 targeted therapies [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-35.
    • 4 Waltzman RJ, Sarkar A, Williams ET, Iberg AT, Higgins JT, Willert EK. MT-5111: A novel HER2 targeting engineered toxin body in clinical development. J Clin Oncol 2020; 38(4_suppl): 433-433.
    • MVC-101
    • EGFR
    • 4 A Dose Escalation and Expansion Study of MVC-101 in Patients With Advanced Cancer [NCT04844073]
    • Margetuximab
    • ERBB2
    • 4 Bang YJ, Giaccone G, Im SA, Oh DY, Bauer TM, Nordstrom JL, Li H, Chichili GR, Moore PA, Hong S, Stewart SJ, Baughman JE, Lechleider RJ, Burris HA. First-in-human phase 1 study of margetuximab (MGAH22), an Fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors. Ann Oncol 2017; 28:855-861.
    • Margetuximab + Capecitabine
    • ERBB2
    • 2 Rugo HS, Im S, Wright GLS, Escriva-de-Romani S, DeLaurentiis M, Cortes J, Bahadur SW, Haley BB, Oyola RH, Riseberg DA, Musolino A, Cardoso F, Curigliano G, Kaufman PA, Pegram MD, Edlich S, Hong S, Rock EP, Gradishar WJ. SOPHIA primary analysis: A phase 3 (P3) study of margetuximab (M) + chemotherapy (C) versus trastuzumab (T) + C in patients (pts) with HER2+ metastatic (met) breast cancer (MBC) after prior anti-HER2 therapies (Tx). J Clin Oncol 2019; 37(15_suppl): 1000-1000.
    • Margetuximab + Eribulin
    • ERBB2
    • 2 Rugo HS, Im S, Wright GLS, Escriva-de-Romani S, DeLaurentiis M, Cortes J, Bahadur SW, Haley BB, Oyola RH, Riseberg DA, Musolino A, Cardoso F, Curigliano G, Kaufman PA, Pegram MD, Edlich S, Hong S, Rock EP, Gradishar WJ. SOPHIA primary analysis: A phase 3 (P3) study of margetuximab (M) + chemotherapy (C) versus trastuzumab (T) + C in patients (pts) with HER2+ metastatic (met) breast cancer (MBC) after prior anti-HER2 therapies (Tx). J Clin Oncol 2019; 37(15_suppl): 1000-1000.
    • Margetuximab + Gemcitabine
    • ERBB2
    • 2 Rugo HS, Im S, Wright GLS, Escriva-de-Romani S, DeLaurentiis M, Cortes J, Bahadur SW, Haley BB, Oyola RH, Riseberg DA, Musolino A, Cardoso F, Curigliano G, Kaufman PA, Pegram MD, Edlich S, Hong S, Rock EP, Gradishar WJ. SOPHIA primary analysis: A phase 3 (P3) study of margetuximab (M) + chemotherapy (C) versus trastuzumab (T) + C in patients (pts) with HER2+ metastatic (met) breast cancer (MBC) after prior anti-HER2 therapies (Tx). J Clin Oncol 2019; 37(15_suppl): 1000-1000.
    • Margetuximab + Pembrolizumab
    • ERBB2
    • 3 Catenacci DVT, Kang YK, Park H, Uronis HE, Lee KW, Ng MCH, Enzinger PC, Park SH, Gold PJ, Lacy J, Hochster HS, Oh SC, Kim YH, Marrone KA, Kelly RJ, Juergens RA, Kim JG, Bendell JC, Alcindor T, Sym SJ, Song EK, Chee CE, Chao Y, Kim S, Lockhart AC, Knutson KL, Yen J, Franovic A, Nordstrom JL, Li D, Wigginton J, Davidson-Moncada JK, Rosales MK, Bang YJ; CP-MGAH22-5 Study Group. Margetuximab plus pembrolizumab in patients with previously treated, HER2-positive gastro-oesophageal adenocarcinoma (CP-MGAH22-05): a single-arm, phase 1b-2 trial. Lancet Oncol 2020; 21:1066-1076.
    • Margetuximab + Vinorelbine
    • ERBB2
    • 2 Rugo HS, Im S, Wright GLS, Escriva-de-Romani S, DeLaurentiis M, Cortes J, Bahadur SW, Haley BB, Oyola RH, Riseberg DA, Musolino A, Cardoso F, Curigliano G, Kaufman PA, Pegram MD, Edlich S, Hong S, Rock EP, Gradishar WJ. SOPHIA primary analysis: A phase 3 (P3) study of margetuximab (M) + chemotherapy (C) versus trastuzumab (T) + C in patients (pts) with HER2+ metastatic (met) breast cancer (MBC) after prior anti-HER2 therapies (Tx). J Clin Oncol 2019; 37(15_suppl): 1000-1000.
    • Medroxyprogesterone Acetate
    • PGR
    • 1 McGuire WL, Horwitz KB, Pearson OH, Segaloff A. Current status of estrogen and progesterone receptors in breast cancer. Cancer 1977; 39(6 Suppl):2934-47.
    • 1 Kiang DT, Kennedy BJ. Tamoxifen (antiestrogen) therapy in advanced breast cancer. Ann Intern Med 1977; 87:687-90.
    • ESR1, PGR
    • 1 A randomized crossover trial in postmenopausal patients with advanced breast cancer. Oral high-dose medroxyprogesterone acetate versus tamoxifen.. Cancer 1986; 58:7-13.
    • 1 Muss HB, Wells HB, Paschold EH, Black WR, Cooper MR, Capizzi RL, Christian R, Cruz JM, Jackson DV, Powell BL, et al. Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association. J Clin Oncol 1988; 6:1098-106.
    • 1 Stuart NS, Warwick J, Blackledge GR, Spooner D, Keen C, Taylor AR, Tyrell C, Webster DJ, Earl H. A randomised phase III cross-over study of tamoxifen versus megestrol acetate in advanced and recurrent breast cancer. Eur J Cancer 1996; 32A:1888-92.
    • PGR
    • 1 Taylor CW, Green S, Dalton WS, Martino S, Rector D, Ingle JN, Robert NJ, Budd GT, Paradelo JC, Natale RB, Bearden JD, Mailliard JA, Osborne CK. Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer: an intergroup study. J Clin Oncol 1998; 16:994-9.
    • 1 Thigpen JT, Brady MF, Alvarez RD, Adelson MD, Homesley HD, Manetta A, Soper JT, Given FT. Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol 1999; 17:1736-44.
    • 1 The Exemestane Study Group. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial.. J Clin Oncol 2000; 18:1399-411.
    • 1 Mouridsen H, Gershanovich M, Sun Y, Pérez-Carrión R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Jänicke F, Pluzanska A, Dank M, Becquart D, Bapsy PP, Salminen E, Snyder R, Lassus M, Verbeek JA, Staffler B, Chaudri-Ross HA, Dugan M. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 2001; 19:2596-606.
    • 1 Bonneterre J, Buzdar A, Nabholtz JM, Robertson JF, Thürlimann B, von Euler M, Sahmoud T, Webster A, Steinberg M; Arimidex Writing Committee; Investigators Committee Members. Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma. Cancer 2001; 92:2247-58.
    • Midostaurin
    • KIT
    • R2 Apsel Winger B, Cortopassi WA, Garrido Ruiz D, Ding L, Jang K, Leyte-Vidal A, Zhang N, Esteve-Puig R, Jacobson MP, Shah NP. ATP-Competitive Inhibitors Midostaurin and Avapritinib Have Distinct Resistance Profiles in Exon 17-Mutant KIT. Cancer Res 2019; 79:4283-4292.
    • FLT3
    • 1 Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, Thiede C, Prior TW, Döhner K, Marcucci G, Lo-Coco F, Klisovic RB, Wei A, Sierra J, Sanz MA, Brandwein JM, de Witte T, Niederwieser D, Appelbaum FR, Medeiros BC, Tallman MS, Krauter J, Schlenk RF, Ganser A, Serve H, Ehninger G, Amadori S, Larson RA, Döhner H. Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation. N Engl J Med 2017; 377:454-464.
    • KIT
    • 4 Apsel Winger B, Cortopassi WA, Garrido Ruiz D, Ding L, Jang K, Leyte-Vidal A, Zhang N, Esteve-Puig R, Jacobson MP, Shah NP. ATP-Competitive Inhibitors Midostaurin and Avapritinib Have Distinct Resistance Profiles in Exon 17-Mutant KIT. Cancer Res 2019; 79:4283-4292.
    • Milademetan Tosylate
    • MDM2
    • 4 Gounder M, Bauer T, Schwartz G, LoRusso P, Kumar P, Kato K, Tao B, Hong Y, Patel P, Hong D. Milademetan, an oral MDM2 inhibitor, in well-differentiated/ dedifferentiated liposarcoma: results from a phase 1 study in patients with solid tumors or lymphomas. E J Cancer 2020; 138 (2): S3. 10.1016/S0959-8049(20)31080-7
    • 4 Bauer TM, Gounder MM, Weise AM, Schwartz GK, Carvajal RD, Kumar P, Zernovak O, Beck A, Doyle J, Mendell-Harary J, Kochan JP, Chen S, LoRusso P, Tap WD, Somaiah N, Hyman DM, Meric-Bernstam F, Hong DS. A phase 1 study of MDM2 inhibitor DS-3032b in patients with well/de-differentiated liposarcoma (WD/DD LPS), solid tumors (ST) and lymphomas (L). J Clin Oncol 2018; 36(15_suppl): 11514-11514.
    • Mirdametinib
    • NF1
    • 3 Weiss BD, Wolters PL, Plotkin SR, Widemann BC, Tonsgard JH, Blakeley J, Allen JC, Schorry E, Korf B, Robison NJ, Goldman S, Vinks AA, Emoto C, Fukuda T, Robinson CT, Cutter G, Edwards L, Dombi E, Ratner N, Packer R, Fisher MJ. NF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults With NF1-Related Plexiform Neurofibromas. J Clin Oncol 2021 Jan 28:JCO2002220. [Epub ahead of print]
    • KRAS
    • 4 White Y, Bagchi A, Van Ziffle J, Inguva A, Bollag G, Zhang C, Carias H, Dickens D, Loh M, Shannon K, Firestone AJ. KRAS insertion mutations are oncogenic and exhibit distinct functional properties. Nat Commun 2016; 7:10647.
    • Mirdametinib + JQ1
    • NF1+SUZ12
    • 4 De Raedt T, Beert E, Pasmant E, Luscan A, Brems H, Ortonne N, Helin K, Hornick JL, Mautner V, Kehrer-Sawatzki H, Clapp W, Bradner J, Vidaud M, Upadhyaya M, Legius E, Cichowski K. PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature 2014; 514:247-51.
    • Mirvetuximab soravtansine
    • FOLR1
    • 3 Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol 2021; 32:757-765.
    • FOLR1
    • 4 Gilbert L, Oaknin A, Matulonis UA, Mantia-Smaldone G, Lim PC, Castro CM, Provencher DM, Memarzadeh S, Wang J, Esteves B, Zweidler-McKay PA, Moore KN, O'Malley DM. Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-agnostic ovarian cancer. J Clin Oncol 2020; 38(15_suppl): 6004-6004.
    • Mirvetuximab soravtansine + Bevacizumab
    • FOLR1
    • 3 O'Malley DM, Oaknin A, Matulonis UA, Mantia-Smaldone G, Lim PC, Castro CM, Provencher DM, Memarzadeh S, Zweidler-McKay PA, Wang J, Esteves B, Moore KN, Gilbert L. Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-agnostic ovarian cancer: Final analysis. J Clin Oncol 2021; 39(15_suppl): 5504-5504.
    • Mivebresib
    • AR
    • 4 Faivre EJ, Wilcox D, Lin X, Hessler P, Torrent M, He W, Uziel T, Albert DH, McDaniel K, Kati W, Shen Y. Exploitation of Castration-Resistant Prostate Cancer Transcription Factor Dependencies by the Novel BET Inhibitor ABBV-075. Mol Cancer Res 2017; 15:35-44.
    • Mobocertinib
    • EGFR
    • R2 Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 2021; 597:732-737.
    • EGFR
    • 2 Riely GJ, Neal JW, Camidge DR, Spira AI, Piotrowska Z, Costa DB, Tsao AS, Patel JD, Gadgeel SM, Bazhenova L, Zhu VW, West HL, Mekhail T, Gentzler RD, Nguyen D, Vincent S, Zhang S, Lin J, Bunn V, Jin S, Li S, Janne PA. Activity and Safety of Mobocertinib (TAK-788) in Previously Treated Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations From a Phase 1/2 Trial. Cancer Discov 2021 Feb 25. pii: candisc.1598.2020. [Epub ahead of print]
    • EGFR
    • 3 Ramalingam SS, Zhou C, Kim TM, Kim S, Yang JC, Riely GJ, Mekhail T, Nguyen D, Campelo MRG, Felip E, Vincent S, Jin S, Bunn V, Lin J, Lin HM, Mehta M, Janne PA, Limited PC, Cambridge , Institute MDC, Boston , MA . Mobocertinib (TAK-788) in EGFR exon 20 insertion (ex20ins)+ metastatic NSCLC (mNSCLC): Additional results from platinum-pretreated patients (pts) and EXCLAIM cohort of phase 1/2 study. J Clin Oncol 2021; 39(15_suppl): 9014-9014.
    • EGFR
    • 4 Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 2021; 597:732-737.
    • Mogamulizumab
    • CCR4
    • 1B Kim YH, Bagot M, Pinter-Brown L, Rook AH, Porcu P, Horwitz SM, Whittaker S, Tokura Y, Vermeer M, Zinzani PL, Sokol L, Morris S, Kim EJ, Ortiz-Romero PL, Eradat H, Scarisbrick J, Tsianakas A, Elmets C, Dalle S, Fisher DC, Halwani A, Poligone B, Greer J, Fierro MT, Khot A, Moskowitz AJ, Musiek A, Shustov A, Pro B, Geskin LJ, Dwyer K, Moriya J, Leoni M, Humphrey JS, Hudgens S, Grebennik DO, Tobinai K, Duvic M; MAVORIC Investigators. Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol 2018; 19:1192-1204.
    • Molibresib
    • ARID1A
    • 4 Berns K, Caumanns JJ, Hijmans EM, Gennissen AMC, Severson TM, Evers B, Wisman GBA, Jan Meersma G, Lieftink C, Beijersbergen RL, Itamochi H, van der Zee AGJ, de Jong S, Bernards R. ARID1A mutation sensitizes most ovarian clear cell carcinomas to BET inhibitors. Oncogene 2018; 37:4611-4625.
    • mRNA-5671
    • KRAS
    • R2 A Study of mRNA-5671/V941 as Monotherapy and in Combination With Pembrolizumab (V941-001) [NCT03948763]
    • N
    • NRR2Mab
    • NOTCH2
    • 4 Hayashi T, Gust KM, Wyatt AW, Goriki A, Jäger W, Awrey S, Li N, Oo HZ, Altamirano-Dimas M, Buttyan R, Fazli L, Matsubara A, Black PC. Not all NOTCH Is Created Equal: The Oncogenic Role of NOTCH2 in Bladder Cancer and Its Implications for Targeted Therapy. Clin Cancer Res 2016; 22:2981-92.
    • Nab-sirolimus
    • TSC2
    • 2 Wagner AJ, Ravi V, Riedel RF, Ganjoo K, Van Tine BA, Chugh R, Cranmer L, Gordon EM, Hornick JL, Du H, Grigorian B, Schmid AN, Hou S, Harris K, Kwiatkowski DJ, Desai NP, Dickson MA. nab-Sirolimus for Patients With Malignant Perivascular Epithelioid Cell Tumors. J Clin Oncol 2021 Oct 12:JCO2101728. [Epub ahead of print]
    • TSC1, TSC2
    • 4 Dickson MA, Ravi V, Ganjoo KN, Iyer G. Institutional experience with nab-sirolimus in patients with malignancies harboring TSC1 or TSC2 mutations. J Clin Oncol 2021; 39(15_suppl): 3111-3111.
    • Navtemadlin
    • TP53
    • 3 . . [DOI:]
    • Nazartinib
    • EGFR
    • R2 Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 2021; 597:732-737.
    • EGFR
    • 4 Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 2021; 597:732-737.
    • Neratinib
    • EGFR
    • R1 Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong KK, Meyerson M, Eck MJ. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A 2008; 105:2070-5.
    • R1 Yasuda H, Kobayashi S, Costa DB. EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications. Lancet Oncol 2012; 13:e23-31.
    • ERBB2
    • R2 Jamunarani Veeraraghavan, Ragini Mistry, Sarmistha Nanda, Vidyalakshmi Sethunath, Martin Shea, Tamika Mitchell, Meenakshi Anurag, Michael A. Mancini, Fabio Stossi, C. Kent Osborne, Mothaffar F. Rimawi, Rachel Schiff. HER2 L755S mutation is acquired upon resistance to lapatinib and neratinib and confers cross-resistance to tucatinib and trastuzumab in HER2-positive breast cancer cell models [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD3-09.
    • ERBB3
    • R2 Hyman DM, Piha-Paul SA, Won H, Rodon J, Saura C, Shapiro GI, Juric D, Quinn DI, Moreno V, Doger B, Mayer IA, Boni V, Calvo E, Loi S, Lockhart AC, Erinjeri JP, Scaltriti M, Ulaner GA, Patel J, Tang J, Beer H, Selcuklu SD, Hanrahan AJ, Bouvier N, Melcer M, Murali R, Schram AM, Smyth LM, Jhaveri K, Li BT, Drilon A, Harding JJ, Iyer G, Taylor BS, Berger MF, Cutler RE Jr, Xu F, Butturini A, Eli LD, Mann G, Farrell C, Lalani AS, Bryce RP, Arteaga CL, Meric-Bernstam F, Baselga J, Solit DB. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature 2018; 554:189-194.
    • ERBB2
    • R2 Robichaux JP, Elamin YY, Vijayan RSK, Nilsson MB, Hu L, He J, Zhang F, Pisegna M, Poteete A, Sun H, Li S, Chen T, Han H, Negrao MV, Ahnert JR, Diao L, Wang J, Le X, Meric-Bernstam F, Routbort M, Roeck B, Yang Z, Raymond VM, Lanman RB, Frampton GM, Miller VA, Schrock AB, Albacker LA, Wong KK, Cross JB, Heymach JV. Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 Activity. Cancer Cell 2019; 36:444-457.e7.
    • R2 Smyth LM, Piha-Paul SA, Won HH, Schram AM, Saura C, Loi S, Lu J, Shapiro GI, Juric D, Mayer IA, Arteaga CL, de la Fuente MI, Brufksy AM, Spanggaard I, Mau-Sørensen M, Arnedos M, Moreno V, Boni V, Sohn J, Schwartzberg LS, Gonzàlez-Farré X, Cervantes A, Bidard FC, Gorelick AN, Lanman RB, Nagy RJ, Ulaner GA, Chandarlapaty S, Jhaveri K, Gavrila EI, Zimel C, Selcuklu SD, Melcer M, Samoila A, Cai Y, Scaltriti M, Mann G, Xu F, Eli LD, Dujka M, Lalani AS, Bryce R, Baselga J, Taylor BS, Solit DB, Meric-Bernstam F, Hyman DM. Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer. Cancer Discov 2020; 10:198-213.
    • EGFR
    • R2 Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 2021; 597:732-737.
    • ERBB2
    • 3 Hyman DM, Piha-Paul SA, Won H, Rodon J, Saura C, Shapiro GI, Juric D, Quinn DI, Moreno V, Doger B, Mayer IA, Boni V, Calvo E, Loi S, Lockhart AC, Erinjeri JP, Scaltriti M, Ulaner GA, Patel J, Tang J, Beer H, Selcuklu SD, Hanrahan AJ, Bouvier N, Melcer M, Murali R, Schram AM, Smyth LM, Jhaveri K, Li BT, Drilon A, Harding JJ, Iyer G, Taylor BS, Berger MF, Cutler RE Jr, Xu F, Butturini A, Eli LD, Mann G, Farrell C, Lalani AS, Bryce RP, Arteaga CL, Meric-Bernstam F, Baselga J, Solit DB. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature 2018; 554:189-194.
    • ERBB2
    • 4 Bose R, Kavuri SM, Searleman AC, Shen W, Shen D, Koboldt DC, Monsey J, Goel N, Aronson AB, Li S, Ma CX, Ding L, Mardis ER, Ellis MJ. Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer Discov 2013; 3:224-37.
    • 4 Hyman DM, Piha-Paul SA, Won H, Rodon J, Saura C, Shapiro GI, Juric D, Quinn DI, Moreno V, Doger B, Mayer IA, Boni V, Calvo E, Loi S, Lockhart AC, Erinjeri JP, Scaltriti M, Ulaner GA, Patel J, Tang J, Beer H, Selcuklu SD, Hanrahan AJ, Bouvier N, Melcer M, Murali R, Schram AM, Smyth LM, Jhaveri K, Li BT, Drilon A, Harding JJ, Iyer G, Taylor BS, Berger MF, Cutler RE Jr, Xu F, Butturini A, Eli LD, Mann G, Farrell C, Lalani AS, Bryce RP, Arteaga CL, Meric-Bernstam F, Baselga J, Solit DB. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature 2018; 554:189-194.
    • 4 Nagano M, Kohsaka S, Ueno T, Kojima S, Saka K, Iwase H, Kawazu M, Mano H. High-Throughput Functional Evaluation of Variants of Unknown Significance in ERBB2. Clin Cancer Res 2018; 24:5112-5122.
    • 4 Pahuja KB, Nguyen TT, Jaiswal BS, Prabhash K, Thaker TM, Senger K, Chaudhuri S, Kljavin NM, Antony A, Phalke S, Kumar P, Mravic M, Stawiski EW, Vargas D, Durinck S, Gupta R, Khanna-Gupta A, Trabucco SE, Sokol ES, Hartmaier RJ, Singh A, Chougule A, Trivedi V, Dutt A, Patil V, Joshi A, Noronha V, Ziai J, Banavali SD, Ramprasad V, DeGrado WF, Bueno R, Jura N, Seshagiri S. Actionable Activating Oncogenic ERBB2/HER2 Transmembrane and Juxtamembrane Domain Mutations. Cancer Cell 2018; 34:792-806.e5.
    • 4 Robichaux JP, Elamin YY, Vijayan RSK, Nilsson MB, Hu L, He J, Zhang F, Pisegna M, Poteete A, Sun H, Li S, Chen T, Han H, Negrao MV, Ahnert JR, Diao L, Wang J, Le X, Meric-Bernstam F, Routbort M, Roeck B, Yang Z, Raymond VM, Lanman RB, Frampton GM, Miller VA, Schrock AB, Albacker LA, Wong KK, Cross JB, Heymach JV. Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 Activity. Cancer Cell 2019; 36:444-457.e7.
    • 4 Gaibar M, Beltrán L, Romero-Lorca A, Fernández-Santander A, Novillo A. Somatic Mutations in HER2 and Implications for Current Treatment Paradigms in HER2-Positive Breast Cancer. J Oncol 2020; 2020:6375956. eCollection 2020.
    • EGFR
    • 4 Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 2021; 597:732-737.
    • Neratinib + Capecitabine
    • ERBB2
    • 2 Saura C, Oliveira M, Feng Y, Dai M, Hurvitz SA, Kim S, Moy B, Delaloge S, Gradishar WJ, Masuda N, Palacova M, Trudeau ME, Mattson J, Yap YS, Bryce R, Yao B, Bebchuk JD, Keyvanjah K, Brufsky A. Neratinib + capecitabine versus lapatinib + capecitabine in patients with HER2+ metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: Findings from the multinational, randomized, phase III NALA trial. J Clin Oncol 2019; 37(15_suppl): 1002-1002.
    • Nilotinib
    • ABL1
    • R1 Nardi V, Azam M, Daley GQ. Mechanisms and implications of imatinib resistance mutations in BCR-ABL. Curr Opin Hematol 2004; 11:35-43.
    • R1 Redaelli S, Piazza R, Rostagno R, Magistroni V, Perini P, Marega M, Gambacorti-Passerini C, Boschelli F. Activity of bosutinib, dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants. J Clin Oncol 2009; 27:469-71.
    • R1 Khoury HJ, Cortes JE, Kantarjian HM, Gambacorti-Passerini C, Baccarani M, Kim DW, Zaritskey A, Countouriotis A, Besson N, Leip E, Kelly V, Brümmendorf TH. Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. Blood 2012; 119:3403-12.
    • R1 Jiang Q, Qin YZ, Lai YY, Jiang H, Wang J, Huang XJ. Patients with Philadelphia-positive leukemia with Y253H or F359V mutation have a high risk of developing new mutations in the setting of dasatinib resistance. Leuk Lymphoma 2015; 56:2075-81.
    • PDGFRA
    • R2 Metzgeroth G, Erben P, Martin H, Mousset S, Teichmann M, Walz C, Klippstein T, Hochhaus A, Cross NC, Hofmann WK, Reiter A. Limited clinical activity of nilotinib and sorafenib in FIP1L1-PDGFRA positive chronic eosinophilic leukemia with imatinib-resistant T674I mutation. Leukemia 2012; 26:162-4.
    • KIT
    • R2 Lee SJ, Kim TM, Kim YJ, Jang KT, Lee HJ, Lee SN, Ahn MS, Hwang IG, Lee S, Lee MH, Lee J. Phase II Trial of Nilotinib in Patients With Metastatic Malignant Melanoma Harboring KIT Gene Aberration: A Multicenter Trial of Korean Cancer Study Group (UN10-06). Oncologist 2015; 20:1312-9.
    • BAP1, NF1, PTPN11, WT1
    • R2 Bigenzahn JW, Collu GM, Kartnig F, Pieraks M, Vladimer GI, Heinz LX, Sedlyarov V, Schischlik F, Fauster A, Rebsamen M, Parapatics K, Blomen VA, Müller AC, Winter GE, Kralovics R, Brummelkamp TR, Mlodzik M, Superti-Furga G. LZTR1 is a regulator of RAS ubiquitination and signaling. Science 2018; 362:1171-1177.
    • ABL1
    • 1 Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, Gallagher N, Hoenekopp A, Dong M, Haque A, Larson RA, Kantarjian HM; ENESTnd Investigators. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010; 362:2251-9.
    • ABL1
    • 2 Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, Bochinski K, Hochhaus A, Griffin JD, Hoelzer D, Albitar M, Dugan M, Cortes J, Alland L, Ottmann OG. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med 2006; 354:2542-51.
    • 2 Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, Gallagher N, Hoenekopp A, Dong M, Haque A, Larson RA, Kantarjian HM; ENESTnd Investigators. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010; 362:2251-9.
    • KIT
    • 3 Sawaki A, Nishida T, Doi T, Yamada Y, Komatsu Y, Kanda T, Kakeji Y, Onozawa Y, Yamasaki M, Ohtsu A. Phase 2 study of nilotinib as third-line therapy for patients with gastrointestinal stromal tumor. Cancer 2011; 117:4633-41.
    • 3 Lee SJ, Kim TM, Kim YJ, Jang KT, Lee HJ, Lee SN, Ahn MS, Hwang IG, Lee S, Lee MH, Lee J. Phase II Trial of Nilotinib in Patients With Metastatic Malignant Melanoma Harboring KIT Gene Aberration: A Multicenter Trial of Korean Cancer Study Group (UN10-06). Oncologist 2015; 20:1312-9.
    • CSF1
    • 3 Gelderblom H, Cropet C, Chevreau C, Boyle R, Tattersall M, Stacchiotti S, Italiano A, Piperno-Neumann S, Le Cesne A, Ferraresi V, Penel N, Duffaud F, Cassier P, Toulmonde M, Casali P, Taieb S, Guillemaut S, Metzger S, Pérol D, Blay JY. Nilotinib in locally advanced pigmented villonodular synovitis: a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol 2018; 19:639-648.
    • Nimotuzumab + Gemcitabine
    • KRAS
    • 2 . . [DOI:]
    • KRAS
    • 4 Schultheis B, Reuter D, Ebert MP, Siveke J, Kerkhoff A, Berdel WE, Hofheinz R, Behringer DM, Schmidt WE, Goker E, De Dosso S, Kneba M, Yalcin S, Overkamp F, Schlegel F, Dommach M, Rohrberg R, Steinmetz T, Bulitta M, Strumberg D. Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen in KRAS wildtype patients with locally advanced or metastatic pancreatic cancer: a multicenter, randomized phase IIb study. Ann Oncol 2017; 28:2429-2435.
    • Niraparib
    • BRCA1, BRCA2
    • 1B González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O'Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Pérez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med 2019; 381:2391-2402.
    • BAP1
    • R2 . . [DOI:]
    • Homologous Recombination Deficiency Score
    • 2 González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O'Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Pérez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med 2019; 381:2391-2402.
    • BRCA1, BRCA2
    • 3 Smith MR, Scher HI, Sandhu S, Efstathiou E, Lara PN Jr, Yu EY, George DJ, Chi KN, Saad F, Ståhl O, Olmos D, Danila DC, Mason GE, Espina BM, Zhao X, Urtishak KA, Francis P, Lopez-Gitlitz A, Fizazi K; GALAHAD investigators. Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial. Lancet Oncol 2022 Feb 4. pii: S1470-2045(21)00757-9. [Epub ahead of print]
    • BAP1
    • 4 A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001) [NCT03207347]
    • 4 Yu H, Pak H, Hammond-Martel I, Ghram M, Rodrigue A, Daou S, Barbour H, Corbeil L, Hébert J, Drobetsky E, Masson JY, Di Noia JM, Affar el B. Tumor suppressor and deubiquitinase BAP1 promotes DNA double-strand break repair. Proc Natl Acad Sci U S A 2014; 111:285-90.
    • 4 Ismail IH, Davidson R, Gagné JP, Xu ZZ, Poirier GG, Hendzel MJ. Germline mutations in BAP1 impair its function in DNA double-strand break repair. Cancer Res 2014; 74:4282-94.
    • Nirogacestat
    • APC, CTNNB1
    • 3 Kummar S, O'Sullivan Coyne G, Do KT, Turkbey B, Meltzer PS, Polley E, Choyke PL, Meehan R, Vilimas R, Horneffer Y, Juwara L, Lih A, Choudhary A, Mitchell SA, Helman LJ, Doroshow JH, Chen AP. Clinical Activity of the γ-Secretase Inhibitor PF-03084014 in Adults With Desmoid Tumors (Aggressive Fibromatosis). J Clin Oncol 2017; 35:1561-1569.
    • NOTCH1
    • 3 Kieran R, de Paula BHR, Hubank M, Barker A, Paterson AL, Gilligan D, Doherty GJ. Response of NOTCH1-Activated Tracheal Adenoid Cystic Carcinoma to the Gamma Secretase Inhibitor Nirogacestat. JCO Precis Oncol 2021; 5:1579-1583.
    • Nivolumab
    • EGFR
    • R2 Lee CK, Man J, Lord S, Cooper W, Links M, Gebski V, Herbst RS, Gralla RJ, Mok T, Yang JC. Clinical and Molecular Characteristics Associated With Survival Among Patients Treated With Checkpoint Inhibitors for Advanced Non-Small Cell Lung Carcinoma: A Systematic Review and Meta-analysis. JAMA Oncol 2018; 4:210-216.
    • ALK
    • R2 Mazieres J, Drilon A, Lusque A, Mhanna L, Cortot AB, Mezquita L, Thai AA, Mascaux C, Couraud S, Veillon R, Van den Heuvel M, Neal J, Peled N, Früh M, Ng TL, Gounant V, Popat S, Diebold J, Sabari J, Zhu VW, Rothschild SI, Bironzo P, Martinez-Marti A, Curioni-Fontecedro A, Rosell R, Lattuca-Truc M, Wiesweg M, Besse B, Solomon B, Barlesi F, Schouten RD, Wakelee H, Camidge DR, Zalcman G, Novello S, Ou SI, Milia J, Gautschi O. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol 2019; 30:1321-1328.
    • HLA-A
    • R2 Naranbhai V, Viard M, Dean M, Groha S, Braun DA, Labaki C, Shukla SA, Yuki Y, Shah P, Chin K, Wind-Rotolo M, Mu XJ, Robbins PB, Gusev A, Choueiri TK, Gulley JL, Carrington M. HLA-A*03 and response to immune checkpoint blockade in cancer: an epidemiological biomarker study. Lancet Oncol 2022; 23:172-184.
    • Microsatellite Instability, Mismatch repair
    • 2 Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, Desai J, Hill A, Axelson M, Moss RA, Goldberg MV, Cao ZA, Ledeine JM, Maglinte GA, Kopetz S, André T. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol 2017; 18:1182-1191.
    • POLE
    • 3 Rousseau B, Bieche I, Pasmant E, Simmet V, Hamzaoui N, Masliah-Planchon J, Pouessel D, Bruyas A, Augereau P, Grob J, Rolland F, Saada-Bouzid E, Cohen R, Bouche O, Hoog-Labouret N, Legrand F, Simon C, Lamrani-Ghaouti A, Chevret S, Marabelle A. 526O High activity of nivolumab in patients with pathogenic exonucleasic domain POLE (edPOLE) mutated Mismatch Repair proficient (MMRp) advanced tumours. Ann Oncol 2020; 31 (4): S463. 10.1016/j.annonc.2020.08.640
    • MLH1, MSH2, Mismatch repair
    • 3 Azad NS, Gray RJ, Overman MJ, Schoenfeld JD, Mitchell EP, Zwiebel JA, Sharon E, Streicher H, Li S, McShane LM, Rubinstein L, Patton DR, Williams PM, Coffey B, Hamilton SR, Bahary N, Suga JM, Hatoum H, Abrams JS, Conley BA, Arteaga CL, Harris L, O'Dwyer PJ, Chen AP, Flaherty KT. Nivolumab Is Effective in Mismatch Repair-Deficient Noncolorectal Cancers: Results From Arm Z1D-A Subprotocol of the NCI-MATCH (EAY131) Study. J Clin Oncol 2020; 38:214-222.
    • CD274
    • 4 Özdemir BC, Bohanes P, Bisig B, Missiaglia E, Tsantoulis P, Coukos G, Montemurro M, Homicsko K, Michielin O. Deep Response to Anti-PD-1 Therapy of Metastatic Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumor With CD274/PD-L1 Amplification. JCO Prec Oncol 2018; 10.1200/PO.18.00375 - published online April 25, 2019
    • PMS2
    • 4 Bouffet E, Larouche V, Campbell BB, Merico D, de Borja R, Aronson M, Durno C, Krueger J, Cabric V, Ramaswamy V, Zhukova N, Mason G, Farah R, Afzal S, Yalon M, Rechavi G, Magimairajan V, Walsh MF, Constantini S, Dvir R, Elhasid R, Reddy A, Osborn M, Sullivan M, Hansford J, Dodgshun A, Klauber-Demore N, Peterson L, Patel S, Lindhorst S, Atkinson J, Cohen Z, Laframboise R, Dirks P, Taylor M, Malkin D, Albrecht S, Dudley RW, Jabado N, Hawkins CE, Shlien A, Tabori U. Immune Checkpoint Inhibition for Hypermutant Glioblastoma Multiforme Resulting From Germline Biallelic Mismatch Repair Deficiency. J Clin Oncol 2016; 34:2206-11.
    • Tumour Mutational Burden
    • 4 Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, Felip E, van den Heuvel MM, Ciuleanu TE, Badin F, Ready N, Hiltermann TJN, Nair S, Juergens R, Peters S, Minenza E, Wrangle JM, Rodriguez-Abreu D, Borghaei H, Blumenschein GR Jr, Villaruz LC, Havel L, Krejci J, Corral Jaime J, Chang H, Geese WJ, Bhagavatheeswaran P, Chen AC, Socinski MA; CheckMate 026 Investigators. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med 2017; 376:2415-2426.
    • CD274
    • 4 Kim RD, Chung V, Alese OB, El-Rayes BF, Li D, Al-Toubah TE, Schell MJ, Zhou JM, Mahipal A, Kim BH, Kim DW. A Phase 2 Multi-institutional Study of Nivolumab for Patients With Advanced Refractory Biliary Tract Cancer. JAMA Oncol 2020 Apr 30. [Epub ahead of print]
    • CDK12
    • 4 Antonarakis ES, Isaacsson Velho P, Fu W, Wang H, Agarwal N, Sacristan Santos V, Maughan BL, Pili R, Adra N, Sternberg CN, Vlachostergios PJ, Tagawa ST, Bryce AH, McNatty AL, Reichert ZR, Dreicer R, Sartor O, Lotan TL, Hussain M. CDK12-Altered Prostate Cancer: Clinical Features and Therapeutic Outcomes to Standard Systemic Therapies, Poly (ADP-Ribose) Polymerase Inhibitors, and PD-1 Inhibitors. JCO Precis Oncol 2020;4:370-381.
    • ARID1A, CXCL13
    • 4 Goswami S, Chen Y, Anandhan S, Szabo PM, Basu S, Blando JM, Liu W, Zhang J, Natarajan SM, Xiong L, Guan B, Yadav SS, Saci A, Allison JP, Galsky MD, Sharma P. ARID1A mutation plus CXCL13 expression act as combinatorial biomarkers to predict responses to immune checkpoint therapy in mUCC. Sci Transl Med 2020; 12(548). pii: eabc4220.
    • MSH2
    • 4 Anghileri E, Di Ianni N, Paterra R, Langella T, Zhao J, Eoli M, Patanè M, Pollo B, Cuccarini V, Iavarone A, Rabadan R, Finocchiaro G, Pellegatta S. High tumor mutational burden and T-cell activation are associated with long-term response to anti-PD1 therapy in Lynch syndrome recurrent glioblastoma patient. Cancer Immunol Immunother 2021; 70:831-842.
    • ARID1A, ARID1B, PBRM1, SMARCA4, SMARCB1
    • 4 Botta GP, Kato S, Patel H, Fanta P, Lee S, Okamura R, Kurzrock R. SWI/SNF complex alterations as a biomarker of immunotherapy efficacy in pancreatic cancer. JCI Insight 2021; 6(18). pii: e150453.
    • CDK12
    • 4 Pan E, Cabal A, Javier-DesLoges J, Patel D, Panian J, Lee S, Shaya J, Nonato T, Xu X, Stewart T, Rose B, Shabaik A, Cohen E, Kurzrock R, Tamayo P, McKay RR. Analysis of CDK12 alterations in a pan-cancer database. Cancer Med 2022; 11:753-763.
    • Nivolumab + CAPOX
    • CD274
    • 2 Moehler M, Shitara K, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Bragagnoli AC, Liu T, Schenker M, Yanez P, Tehfe M, Poulart V, Cullen D, Lei M, Kondo K, Li M, Ajani J, Janjigian Y. LBA6_PR Nivolumab (nivo) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC)/esophageal adenocarcinoma (EAC): First results of the CheckMate 649 study. Ann Oncol 2020; 31 (4): S1191. 10.1016/j.annonc.2020.08.2296
    • 2 Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Campos Bragagnoli A, Liu T, Schenker M, Yanez P, Tehfe M, Kowalyszyn R, Karamouzis MV, Bruges R, Zander T, Pazo-Cid R, Hitre E, Feeney K, Cleary JM, Poulart V, Cullen D, Lei M, Xiao H, Kondo K, Li M, Ajani JA. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet 2021; 398:27-40.
    • Nivolumab + FOLFOX
    • CD274
    • 2 Moehler M, Shitara K, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Bragagnoli AC, Liu T, Schenker M, Yanez P, Tehfe M, Poulart V, Cullen D, Lei M, Kondo K, Li M, Ajani J, Janjigian Y. LBA6_PR Nivolumab (nivo) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC)/esophageal adenocarcinoma (EAC): First results of the CheckMate 649 study. Ann Oncol 2020; 31 (4): S1191. 10.1016/j.annonc.2020.08.2296
    • 2 Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Campos Bragagnoli A, Liu T, Schenker M, Yanez P, Tehfe M, Kowalyszyn R, Karamouzis MV, Bruges R, Zander T, Pazo-Cid R, Hitre E, Feeney K, Cleary JM, Poulart V, Cullen D, Lei M, Xiao H, Kondo K, Li M, Ajani JA. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet 2021; 398:27-40.
    • Nivolumab + Fluorouracil + Cisplatin
    • CD274
    • 2 Doki Y, Ajani JA, Kato K, Xu J, Wyrwicz L, Motoyama S, Ogata T, Kawakami H, Hsu CH, Adenis A, El Hajbi F, Di Bartolomeo M, Braghiroli MI, Holtved E, Ostoich SA, Kim HR, Ueno M, Mansoor W, Yang WC, Liu T, Bridgewater J, Makino T, Xynos I, Liu X, Lei M, Kondo K, Patel A, Gricar J, Chau I, Kitagawa Y; CheckMate 648 Trial Investigators. Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. N Engl J Med 2022; 386:449-462.
    • Nivolumab + Ipilimumab
    • CD274+EGFR+ALK
    • 1B Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim SW, Carcereny Costa E, Park K, Alexandru A, Lupinacci L, de la Mora Jimenez E, Sakai H, Albert I, Vergnenegre A, Peters S, Syrigos K, Barlesi F, Reck M, Borghaei H, Brahmer JR, O'Byrne KJ, Geese WJ, Bhagavatheeswaran P, Rabindran SK, Kasinathan RS, Nathan FE, Ramalingam SS. Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. N Engl J Med 2019; 381:2020-2031.
    • Tumour Mutational Burden
    • 2 Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O'Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med 2018; 378:2093-2104.
    • CD274
    • 2 Doki Y, Ajani JA, Kato K, Xu J, Wyrwicz L, Motoyama S, Ogata T, Kawakami H, Hsu CH, Adenis A, El Hajbi F, Di Bartolomeo M, Braghiroli MI, Holtved E, Ostoich SA, Kim HR, Ueno M, Mansoor W, Yang WC, Liu T, Bridgewater J, Makino T, Xynos I, Liu X, Lei M, Kondo K, Patel A, Gricar J, Chau I, Kitagawa Y; CheckMate 648 Trial Investigators. Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. N Engl J Med 2022; 386:449-462.
    • Mismatch repair
    • 4 Noor A, Aguirre LE, Blue K, Avriett T, Carballido EM, Kim RD, Kim DW. Investigate the efficacy of immunotherapy for treatment of pancreatic adenocarcinoma (PDAC) with mismatch repair deficiency (dMMR). J Clin Oncol 2021; 39(3_suppl): 415-415.
    • CDK12
    • 4 Schweizer MT, Ha G, Gulati R, Brown LC, McKay RR, Dorff T, Hoge ACH, Reichel J, Vats P, Kilari D, Patel V, Oh WK, Chinnaiyan A, Pritchard CC, Armstrong AJ, Montgomery RB, Alva A. CDK12-Mutated Prostate Cancer: Clinical Outcomes With Standard Therapies and Immune Checkpoint Blockade. JCO Precis Oncol 2020;4:382-392.
    • 4 Pan E, Cabal A, Javier-DesLoges J, Patel D, Panian J, Lee S, Shaya J, Nonato T, Xu X, Stewart T, Rose B, Shabaik A, Cohen E, Kurzrock R, Tamayo P, McKay RR. Analysis of CDK12 alterations in a pan-cancer database. Cancer Med 2022; 11:753-763.
    • O
    • OP-1250
    • ESR1
    • 4 A Dose Escalation/Expansion Study of Oral OP-1250 in Subjects With Advanced and/or Metastatic HR+, HER2- Breast Cancer [NCT04505826]
    • Obinutuzumab
    • CD20
    • 1 Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the First-Line Treatment of Follicular Lymphoma. N Engl J Med 2017; 377:1331-1344.
    • Octreotide
    • SSTR2
    • 1 Rinke A, Müller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, Mayer C, Aminossadati B, Pape UF, Bläker M, Harder J, Arnold C, Gress T, Arnold R; PROMID Study Group. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 2009; 27:4656-63.
    • 1 Rinke A, Wittenberg M, Schade-Brittinger C, Aminossadati B, Ronicke E, Gress TM, Müller HH, Arnold R; PROMID Study Group. Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients with Metastatic Neuroendocrine Midgut Tumors (PROMID): Results of Long-Term Survival. Neuroendocrinology 2017;104:26-32.
    • Ofatumumab
    • CD20
    • 2 Wierda WG, Kipps TJ, Mayer J, Stilgenbauer S, Williams CD, Hellmann A, Robak T, Furman RR, Hillmen P, Trneny M, Dyer MJ, Padmanabhan S, Piotrowska M, Kozak T, Chan G, Davis R, Losic N, Wilms J, Russell CA, Osterborg A; Hx-CD20-406 Study Investigators. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol 2010; 28:1749-55.
    • Olaparib
    • BRCA1, BRCA2
    • 1 Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 2017; 18:1274-1284.
    • 1 Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian C, Bradley W, Mathews C, Liu J, Lowe ES, Bloomfield R, DiSilvestro P. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med 2018; 379:2495-2505.
    • 1 Poveda A, Floquet A, Ledermann JA, Asher R, Penson RT, Oza AM, Korach J, Huzarski T, Pignata S, Friedlander M, Baldoni A, Park-Simon TW, Tamura K, Sonke GS, Lisyanskaya A, Kim JH, Filho EA, Milenkova T, Lowe ES, Rowe P, Vergote I, Pujade-Lauraine E; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 2021 Mar 18. pii: S1470-2045(21)00073-5. [Epub ahead of print]
    • BRCA1
    • 1 Banerjee S, Moore KN, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Oza A, González-Martín A, Aghajanian C, Bradley WH, Holmes E, Lowe ES, DiSilvestro P. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2021 Oct 26. pii: S1470-2045(21)00531-3. [Epub ahead of print]
    • BRCA1, BRCA2
    • 1B Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med 2017; 377:523-533.
    • 1B Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N Engl J Med 2019; 381:317-327.
    • 1B de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2020; 382:2091-2102.
    • 1B Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Özgüroğlu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2020; 383:2345-2357.
    • ATM, CHEK2
    • R2 Tung NM, Robson ME, Ventz S, Santa-Maria CA, Marcom PK, Nanda R, Shah PD, Ballinger TJ, Yang ES, Melisko ME, Brufsky A, Vinayak S, Demeo M, Jenkins C, Domchek SM, Wulf GM, Krop IE, Wolff AC, Winer EP, Garber JE, MA MSBMCGaPDCIB. TBCRC 048: A phase II study of olaparib monotherapy in metastatic breast cancer patients with germline or somatic mutations in DNA damage response (DDR) pathway genes (Olaparib Expanded). J Clin Oncol 2020; 38(15_suppl): 1002-1002.
    • IDH1
    • R2 Eder JP, Doroshow DB, Do KT, Keedy VL, Sklar JS, Glazer P, Bindra R, Shapiro GI. Clinical Efficacy of Olaparib in IDH1/IDH2-Mutant Mesenchymal Sarcomas. JCO Prec Oncol 2020; 10.1200/PO.20.00247 5 466-472. Published online February 26, 2021.
    • ATM
    • R2 Marshall CH, Sokolova AO, McNatty AL, Cheng HH, Eisenberger MA, Bryce AH, Schweizer MT, Antonarakis ES. Differential Response to Olaparib Treatment Among Men with Metastatic Castration-resistant Prostate Cancer Harboring BRCA1 or BRCA2 Versus ATM Mutations. Eur Urol 2019; 76:452-458.
    • CDK12
    • R2 Mateo J, Porta N, Bianchini D, McGovern U, Elliott T, Jones R, Syndikus I, Ralph C, Jain S, Varughese M, Parikh O, Crabb S, Robinson A, McLaren D, Birtle A, Tanguay J, Miranda S, Figueiredo I, Seed G, Bertan C, Flohr P, Ebbs B, Rescigno P, Fowler G, Ferreira A, Riisnaes R, Pereira R, Curcean A, Chandler R, Clarke M, Gurel B, Crespo M, Nava Rodrigues D, Sandhu S, Espinasse A, Chatfield P, Tunariu N, Yuan W, Hall E, Carreira S, de Bono JS. Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol 2020; 21:162-174.
    • BAP1
    • R2 Rathkey D, Khanal M, Murai J, Zhang J, Sengupta M, Jiang Q, Morrow B, Evans CN, Chari R, Fetsch P, Chung HJ, Xi L, Roth M, Filie A, Raffeld M, Thomas A, Pommier Y, Hassan R. Sensitivity of Mesothelioma Cells to PARP Inhibitors Is Not Dependent on BAP1 but Is Enhanced by Temozolomide in Cells With High-Schlafen 11 and Low-O6-methylguanine-DNA Methyltransferase Expression. J Thorac Oncol 2020; 15:843-859.
    • ATM, CDK12, PPP2R2A
    • R2 de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2020; 382:2091-2102.
    • CDK12
    • R2 Antonarakis ES, Isaacsson Velho P, Fu W, Wang H, Agarwal N, Sacristan Santos V, Maughan BL, Pili R, Adra N, Sternberg CN, Vlachostergios PJ, Tagawa ST, Bryce AH, McNatty AL, Reichert ZR, Dreicer R, Sartor O, Lotan TL, Hussain M. CDK12-Altered Prostate Cancer: Clinical Features and Therapeutic Outcomes to Standard Systemic Therapies, Poly (ADP-Ribose) Polymerase Inhibitors, and PD-1 Inhibitors. JCO Precis Oncol 2020;4:370-381.
    • ATM, CDK12, PPP2R2A
    • R2 Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Özgüroğlu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2020; 383:2345-2357.
    • ATM, CHEK2
    • R2 Tung NM, Robson ME, Ventz S, Santa-Maria CA, Nanda R, Marcom PK, Shah PD, Ballinger TJ, Yang ES, Vinayak S, Melisko M, Brufsky A, DeMeo M, Jenkins C, Domchek S, D'Andrea A, Lin NU, Hughes ME, Carey LA, Wagle N, Wulf GM, Krop IE, Wolff AC, Winer EP, Garber JE. TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes. J Clin Oncol 2020 Oct 29:JCO2002151. [Epub ahead of print]
    • ARID1A, ATM, FANCD2, PTEN, RAD51C
    • R2 Javle M, Shacham-Shmueli E, Xiao L, Varadhachary G, Halpern N, Fogelman D, Boursi B, Uruba S, Margalit O, Wolff RA, Golan T. Olaparib Monotherapy for Previously Treated Pancreatic Cancer With DNA Damage Repair Genetic Alterations Other Than Germline BRCA Variants: Findings From 2 Phase 2 Nonrandomized Clinical Trials. JAMA Oncol 2021 Mar 4. [Epub ahead of print]
    • BAP1
    • R2 Ghafoor A, Mian I, Wagner C, Mallory Y, Agra MG, Morrow B, Wei JS, Khan J, Thomas A, Sengupta M, Steinberg SM, Hassan R. Phase 2 Study of Olaparib in Malignant Mesothelioma and Correlation of Efficacy With Germline or Somatic Mutations in BAP1 Gene. JTO Clin Res Rep 2021; 2:100231. eCollection 2021 Oct.
    • BRCA2
    • 2 Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N Engl J Med 2019; 381:317-327.
    • BRCA1, BRCA2, PALB2
    • 3 Tung NM, Robson ME, Ventz S, Santa-Maria CA, Marcom PK, Nanda R, Shah PD, Ballinger TJ, Yang ES, Melisko ME, Brufsky A, Vinayak S, Demeo M, Jenkins C, Domchek SM, Wulf GM, Krop IE, Wolff AC, Winer EP, Garber JE, MA MSBMCGaPDCIB. TBCRC 048: A phase II study of olaparib monotherapy in metastatic breast cancer patients with germline or somatic mutations in DNA damage response (DDR) pathway genes (Olaparib Expanded). J Clin Oncol 2020; 38(15_suppl): 1002-1002.
    • IDH1
    • 3 Ducray F, Sanson M, Chinot OL, Fontanilles M, Rivoirard R, Thomas-Maisonneuve L, Cartalat S, Tabouret E, Bonneville-Levard A, Darlix A, Ameli R, Meyronet D, Gueyffier F, Remontet L, Maucort-Boulch D, Dehais C, Honnorat J, 5558 , Lyon , (AP-HP) FAPdP, Pitié-Salpêtrière HUL, Neuro-oncology Do, Paris , Wertheimer FHP, Lyon , France . Olaparib in recurrent IDH-mutant high-grade glioma (OLAGLI). J Clin Oncol 2021; 39(15_suppl): 2007-2007.
    • IDH2
    • 3 Eder JP, Doroshow DB, Do KT, Keedy VL, Sklar JS, Glazer P, Bindra R, Shapiro GI. Clinical Efficacy of Olaparib in IDH1/IDH2-Mutant Mesenchymal Sarcomas. JCO Prec Oncol 2020; 10.1200/PO.20.00247 5 466-472. Published online February 26, 2021.
    • BRCA1, BRCA2, PALB2
    • 3 Tung NM, Robson ME, Ventz S, Santa-Maria CA, Nanda R, Marcom PK, Shah PD, Ballinger TJ, Yang ES, Vinayak S, Melisko M, Brufsky A, DeMeo M, Jenkins C, Domchek S, D'Andrea A, Lin NU, Hughes ME, Carey LA, Wagle N, Wulf GM, Krop IE, Wolff AC, Winer EP, Garber JE. TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes. J Clin Oncol 2020 Oct 29:JCO2002151. [Epub ahead of print]
    • IDH1
    • 3 Eder JP, Doroshow DB, Do KT, Keedy VL, Sklar JS, Glazer P, Bindra R, Shapiro GI. Clinical Efficacy of Olaparib in IDH1/IDH2-Mutant Mesenchymal Sarcomas. JCO Precis Oncol 2021; 5:466-472.
    • RAD51D
    • 4 Chandran EA, Kennedy I. Significant Tumor Response to the Poly (ADP-ribose) Polymerase Inhibitor Olaparib in Heavily Pretreated Patient With Ovarian Carcinosarcoma Harboring a Germline RAD51D Mutation. JCO Prec Oncol 2018; 10.1200/PO.18.00253
    • BRCA1
    • 4 Pascual T, Gonzalez-Farre B, Teixidó C, Oleaga L, Oses G, Ganau S, Chic N, Riu G, Adamo B, Galván P, Vidal M, Soy D, Urbano , Muñoz M, Prat A. Significant Clinical Activity of Olaparib in a Somatic BRCA1-Mutated Triple-Negative Breast Cancer With Brain Metastasis. JCO Prec Oncol 2019; 10.1200/PO.19.00012 - published online June 7, 2019
    • RAD51C
    • 4 Min A, Im SA, Yoon YK, Song SH, Nam HJ, Hur HS, Kim HP, Lee KH, Han SW, Oh DY, Kim TY, O'Connor MJ, Kim WH, Bang YJ. RAD51C-deficient cancer cells are highly sensitive to the PARP inhibitor olaparib. Mol Cancer Ther 2013; 12:865-77.
    • ARID1A
    • 4 Shen J, Peng Y, Wei L, Zhang W, Yang L, Lan L, Kapoor P, Ju Z, Mo Q, Shih IeM, Uray IP, Wu X, Brown PH, Shen X, Mills GB, Peng G. ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors. Cancer Discov 2015; 5:752-67.
    • ATM
    • 4 Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, Nava Rodrigues D, Robinson D, Omlin A, Tunariu N, Boysen G, Porta N, Flohr P, Gillman A, Figueiredo I, Paulding C, Seed G, Jain S, Ralph C, Protheroe A, Hussain S, Jones R, Elliott T, McGovern U, Bianchini D, Goodall J, Zafeiriou Z, Williamson CT, Ferraldeschi R, Riisnaes R, Ebbs B, Fowler G, Roda D, Yuan W, Wu YM, Cao X, Brough R, Pemberton H, A'Hern R, Swain A, Kunju LP, Eeles R, Attard G, Lord CJ, Ashworth A, Rubin MA, Knudsen KE, Feng FY, Chinnaiyan AM, Hall E, de Bono JS. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med 2015; 373:1697-708.
    • RAD50
    • 4 Zhang M, Liu G, Xue F, Edwards R, Sood AK, Zhang W, Yang D. Copy number deletion of RAD50 as predictive marker of BRCAness and PARP inhibitor response in BRCA wild type ovarian cancer. Gynecol Oncol 2016; 141:57-64.
    • SLX4
    • 4 Liu Q, Underwood TSA, Kung J, Wang M, Lu HM, Paganetti H, Held KD, Hong TS, Efstathiou JA, Willers H. Disruption of SLX4-MUS81 Function Increases the Relative Biological Effectiveness of Proton Radiation. Int J Radiat Oncol Biol Phys 2016; 95:78-85.
    • IDH1, IDH2
    • 4 Sulkowski PL, Corso CD, Robinson ND, Scanlon SE, Purshouse KR, Bai H, Liu Y, Sundaram RK, Hegan DC, Fons NR, Breuer GA, Song Y, Mishra-Gorur K, De Feyter HM, de Graaf RA, Surovtseva YV, Kachman M, Halene S, Günel M, Glazer PM, Bindra RS. 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. Sci Transl Med 2017; 9(375). pii: eaal2463.
    • ATM
    • 4 Wang C, Jette N, Moussienko D, Bebb DG, Lees-Miller SP. ATM-Deficient Colorectal Cancer Cells Are Sensitive to the PARP Inhibitor Olaparib. Transl Oncol 2017; 10:190-196.
    • ATM, BARD1, BRCA1, BRCA2, FAM175A, MRE11A, PALB2, RAD50, RAD51C, XRCC2
    • 4 Gravells P, Grant E, Smith KM, James DI, Bryant HE. Specific killing of DNA damage-response deficient cells with inhibitors of poly(ADP-ribose) glycohydrolase. DNA Repair (Amst) 2017; 52:81-91.
    • RAD51D
    • 4 Kondrashova O, Nguyen M, Shield-Artin K, Tinker AV, Teng NNH, Harrell MI, Kuiper MJ, Ho GY, Barker H, Jasin M, Prakash R, Kass EM, Sullivan MR, Brunette GJ, Bernstein KA, Coleman RL, Floquet A, Friedlander M, Kichenadasse G, O'Malley DM, Oza A, Sun J, Robillard L, Maloney L, Bowtell D, Giordano H, Wakefield MJ, Kaufmann SH, Simmons AD, Harding TC, Raponi M, McNeish IA, Swisher EM, Lin KK, Scott CL; AOCS Study Group. Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma. Cancer Discov 2017; 7:984-998.
    • 4 Rivera B, Di Iorio M, Frankum J, Nadaf J, Fahiminiya S, Arcand SL, Burk DL, Grapton D, Tomiak E, Hastings V, Hamel N, Wagener R, Aleynikova O, Giroux S, Hamdan FF, Dionne-Laporte A, Zogopoulos G, Rousseau F, Berghuis AM, Provencher D, Rouleau GA, Michaud JL, Mes-Masson AM, Majewski J, Bens S, Siebert R, Narod SA, Akbari MR, Lord CJ, Tonin PN, Orthwein A, Foulkes WD. Functionally Null RAD51D Missense Mutation Associates Strongly with Ovarian Carcinoma. Cancer Res 2017; 77:4517-4529.
    • ATM
    • 4 Cecchini M, Walther Z, Sklar JL, Bindra RS, Petrylak DP, Eder JP, Goldberg SB. Yale Cancer Center Precision Medicine Tumor Board: two patients, one targeted therapy, different outcomes. Lancet Oncol 2018; 19:23-24.
    • KMT2C
    • 4 Rampias T, Karagiannis D, Avgeris M, Polyzos A, Kokkalis A, Kanaki Z, Kousidou E, Tzetis M, Kanavakis E, Stravodimos K, Manola KN, Pantelias GE, Scorilas A, Klinakis A. The lysine-specific methyltransferase KMT2C/MLL3 regulates DNA repair components in cancer. EMBO Rep 2019; 20(3). pii: e46821.
    • ATM, CHEK1, CHEK2, FANCG, FANCI, NBN
    • 4 Mateo J, Porta N, Bianchini D, McGovern U, Elliott T, Jones R, Syndikus I, Ralph C, Jain S, Varughese M, Parikh O, Crabb S, Robinson A, McLaren D, Birtle A, Tanguay J, Miranda S, Figueiredo I, Seed G, Bertan C, Flohr P, Ebbs B, Rescigno P, Fowler G, Ferreira A, Riisnaes R, Pereira R, Curcean A, Chandler R, Clarke M, Gurel B, Crespo M, Nava Rodrigues D, Sandhu S, Espinasse A, Chatfield P, Tunariu N, Yuan W, Hall E, Carreira S, de Bono JS. Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol 2020; 21:162-174.
    • ATM
    • 4 Zhang W, Shi J, Li R, Han Z, Li L, Li G, Yang B, Yin Q, Wang Y, Ke Y, Li Q. Effectiveness of Olaparib Treatment in a Patient with Gallbladder Cancer with an ATM-Inactivating Mutation. Oncologist 2020; 25:375-379.
    • NBN
    • 4 Abida W, Campbell D, Patnaik A, Shapiro JD, Sautois B, Vogelzang NJ, Voog EG, Bryce AH, McDermott R, Ricci F, Rowe J, Zhang J, Piulats JM, Fizazi K, Merseburger AS, Higano CS, Krieger LE, Ryan CJ, Feng FY, Simmons AD, Loehr A, Despain D, Dowson M, Green F, Watkins SP, Golsorkhi T, Chowdhury S. Non-BRCA DNA Damage Repair Gene Alterations and Response to the PARP Inhibitor Rucaparib in Metastatic Castration-Resistant Prostate Cancer: Analysis From the Phase II TRITON2 Study. Clin Cancer Res 2020; 26:2487-2496.
    • PPM1D
    • 4 Wang Z, Xu C, Diplas BH, Moure CJ, Chen CJ, Chen LH, Du C, Zhu H, Greer PK, Zhang L, He Y, Waitkus MS, Yan H. Targeting Mutant PPM1D Sensitizes Diffuse Intrinsic Pontine Glioma Cells to the PARP Inhibitor Olaparib. Mol Cancer Res 2020; 18:968-980.
    • BARD1, BRIP1, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51D, RAD54L
    • 4 de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2020; 382:2091-2102.
    • IDH1, IDH2
    • 4 Wang Y, Wild AT, Turcan S, Wu WH, Sigel C, Klimstra DS, Ma X, Gong Y, Holland EC, Huse JT, Chan TA. Targeting therapeutic vulnerabilities with PARP inhibition and radiation in IDH-mutant gliomas and cholangiocarcinomas. Sci Adv 2020; 6:eaaz3221. eCollection 2020 Apr.
    • PALB2
    • 4 Kuemmel S, Harrach H, Schmutzler RK, Kostara A, Ziegler-Löhr K, Dyson MH, Chiari O, Reinisch M. Olaparib for metastatic breast cancer in a patient with a germline PALB2 variant. NPJ Breast Cancer 2020; 6:31. eCollection 2020.
    • ATRX
    • 4 George SL, Lorenzi F, King D, Hartlieb S, Campbell J, Pemberton H, Toprak UH, Barker K, Tall J, da Costa BM, van den Boogaard ML, Dolman MEM, Molenaar JJ, Bryant HE, Westermann F, Lord CJ, Chesler L. Therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma. EBioMedicine 2020; 59:102971.
    • BRIP1
    • 4 Nakamura K, Aimono E, Tanishima S, Imai M, Nagatsuma AK, Hayashi H, Yoshimura Y, Nakayama K, Kyo S, Nishihara H. Olaparib Monotherapy for BRIP1-Mutated High-Grade Serous Endometrial Cancer. JCO Precis Oncol 2020; 4. pii: PO.19.00368. eCollection 2020.
    • BARD1, BRIP1, FANCL, PALB2, RAD51B, RAD51D, RAD54L
    • 4 Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Özgüroğlu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2020; 383:2345-2357.
    • PALB2
    • 4 Javle M, Shacham-Shmueli E, Xiao L, Varadhachary G, Halpern N, Fogelman D, Boursi B, Uruba S, Margalit O, Wolff RA, Golan T. Olaparib Monotherapy for Previously Treated Pancreatic Cancer With DNA Damage Repair Genetic Alterations Other Than Germline BRCA Variants: Findings From 2 Phase 2 Nonrandomized Clinical Trials. JAMA Oncol 2021 Mar 4. [Epub ahead of print]
    • PBRM1
    • 4 Chabanon RM, Morel D, Eychenne T, Colmet-Daage L, Bajrami I, Dorvault N, Garrido M, Meisenberg C, Lamb A, Ngo C, Hopkins SR, Roumeliotis TI, Jouny S, Hénon C, Kawai-Kawachi A, Astier C, Konde A, Del Nery E, Massard C, Pettitt SJ, Margueron R, Choudhary JS, Almouzni G, Soria JC, Deutsch E, Downs JA, Lord CJ, Postel-Vinay S. PBRM1 Deficiency Confers Synthetic Lethality to DNA Repair Inhibitors in Cancer. Cancer Res 2021 Apr 22. [Epub ahead of print]
    • MRE11A
    • 4 Ghafoor A, Mian I, Wagner C, Mallory Y, Agra MG, Morrow B, Wei JS, Khan J, Thomas A, Sengupta M, Steinberg SM, Hassan R. Phase 2 Study of Olaparib in Malignant Mesothelioma and Correlation of Efficacy With Germline or Somatic Mutations in BAP1 Gene. JTO Clin Res Rep 2021; 2:100231. eCollection 2021 Oct.
    • Olaparib + Bevacizumab
    • BRCA1, BRCA2
    • 1 Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, Fujiwara K, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alía EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marmé F, Combe P, de Gregorio N, Rodrigues M, Buderath P, Dubot C, Burges A, You B, Pujade-Lauraine E, Harter P; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med 2019; 381:2416-2428.
    • Homologous Recombination Deficiency Score
    • 2 Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, Fujiwara K, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alía EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marmé F, Combe P, de Gregorio N, Rodrigues M, Buderath P, Dubot C, Burges A, You B, Pujade-Lauraine E, Harter P; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med 2019; 381:2416-2428.
    • Olaparib + Ceralasertib
    • ATM, BRCA1, BRCA2, CCNE1, RAD51
    • 4 Ring AE, Moretti L, Afshari-Mehr A, Wardley AM, Kilburn L, Gurel B, MacPherson IR, Baird RD, Martin S, Pearson A, Roylance R, Winter M, Dunne K, Copson E, Hickish T, Stephens P, Burcombe RJ, Randle K, Bliss J, Turner NC, Research , Hospital RM, London , Southampton UKUo, Southampton , Hospital UKRBHaPG, Bournemouth , Hospital UKRDaE, Exeter , Trust UKMaTWN, Kent , Voice UKICP, London , Research UKTIoC, Unit CT&S, London , Research UKRMHaIoC, London , Kingdom U. Results from plasmaMATCH trial cohort E: A phase II trial of olaparib and ceralasertib in patients with triple-negative advanced breast cancer (CRUK/15/010). J Clin Oncol 2022; 40(16_suppl): 1024-1024.
    • Olaparib + Durvalumab
    • BRCA2
    • 3 Domchek SM, Postel-Vinay S, Im SA, Park YH, Delord JP, Italiano A, Alexandre J, You B, Bastian S, Krebs MG, Wang D, Waqar SN, Lanasa M, Rhee J, Gao H, Rocher-Ros V, Jones EV, Gulati S, Coenen-Stass A, Kozarewa I, Lai Z, Angell HK, Opincar L, Herbolsheimer P, Kaufman B. Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Lancet Oncol 2020; 21:1155-1164.
    • Olaratumab
    • PDGFRA
    • R2 Cornillie J, Wozniak A, Van Renterghem B, Van Winkel N, Wellens J, Gebreyohannes YK, Debiec-Rychter M, Sciot R, Hompes D, Schöffski P. Assessment of the platelet-derived growth factor receptor alpha antibody olaratumab in a panel of patient-derived soft tissue sarcoma xenografts. BMC Cancer 2019; 19:724.
    • Olaratumab + Doxorubicin
    • PDGFRA
    • R2 Tap WD, Wagner AJ, Schöffski P, Martin-Broto J, Krarup-Hansen A, Ganjoo KN, Yen CC, Abdul Razak AR, Spira A, Kawai A, Le Cesne A, Van Tine BA, Naito Y, Park SH, Fedenko A, Pápai Z, Soldatenkova V, Shahir A, Mo G, Wright J, Jones RL; ANNOUNCE Investigators. Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial. JAMA 2020; 323:1266-1276.
    • Olutasidenib
    • IDH1
    • 3 Botton SD, Yee KWL, Recher C, Wei A, Montesinos P, Taussig D, Pigneux A, Braun T, Curti A, Esteve J, Grove C, Jonas BA, Khwaja A, Legrand O, Peterlin P, Polyanskaya O, Sweeney J, Mohamed H, Cortes JE, Fenaux P, Saint-Louis H, 7 UP, Paris , France . Effect of olutasidenib (FT-2102) on complete remissions in patients with relapsed/refractory (R/R) mIDH1 acute myeloid leukemia (AML): Results from a planned interim analysis of a phase 2 clinical trial. J Clin Oncol 2021; 39(15_suppl): 7006-7006.
    • IDH1
    • 4 Fuente MIDL, Colman H, Rosenthal M, Tine BAV, Levaci D, Walbert T, Gan HK, Vieito M, Milhem MM, Lipford K, Forsyth S, Guichard SM, Mikhailov Y, Sedkov A, Thomson B, Kelly PF, Monga V. A phase Ib/II study of olutasidenib in patients with relapsed/refractory IDH1 mutant gliomas: Safety and efficacy as single agent and in combination with azacitidine. J Clin Oncol 2020; 38(15_suppl): 2505-2505.
    • Onvansertib
    • KRAS
    • 4 Lenz H, Ahn DH, Ridinger M, Erlander MG, Barzi A. A phase Ib/II study of onvansertib (PCM-075) in combination with FOLFIRI and bevacizumab for second-line treatment of metastatic colorectal cancer (mCRC) in patients with a KRAS mutation. J Clin Oncol 2020; 38(4_suppl):
    • 4 Onvansertib in Combination With FOLFIRI and Bevacizumab for Second Line Treatment of Metastatic Colorectal Cancer Patients With a Kras Mutation [NCT03829410]
    • Onvansertib + FOLFIRI + Bevacizumab
    • KRAS
    • 4 Lenz H, Ahn DH, Ridinger M, Erlander MG, Barzi A. A phase Ib/II study of onvansertib (PCM-075) in combination with FOLFIRI and bevacizumab for second-line treatment of metastatic colorectal cancer (mCRC) in patients with a KRAS mutation. J Clin Oncol 2020; 38(4_suppl):
    • 4 Onvansertib in Combination With FOLFIRI and Bevacizumab for Second Line Treatment of Metastatic Colorectal Cancer Patients With a Kras Mutation [NCT03829410]
    • Osimertinib
    • ALK, BRAF, FGFR3, KRAS, PIK3CA, RET
    • R2 Yu HA, Arcila ME, Rekhtman N, Sima CS, Zakowski MF, Pao W, Kris MG, Miller VA, Ladanyi M, Riely GJ. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res 2013; 19:2240-7.
    • EGFR+RB1
    • R2 Niederst MJ, Sequist LV, Poirier JT, Mermel CH, Lockerman EL, Garcia AR, Katayama R, Costa C, Ross KN, Moran T, Howe E, Fulton LE, Mulvey HE, Bernardo LA, Mohamoud F, Miyoshi N, VanderLaan PA, Costa DB, Jänne PA, Borger DR, Ramaswamy S, Shioda T, Iafrate AJ, Getz G, Rudin CM, Mino-Kenudson M, Engelman JA. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat Commun 2015; 6:6377.
    • EGFR
    • R2 Niederst MJ, Hu H, Mulvey HE, Lockerman EL, Garcia AR, Piotrowska Z, Sequist LV, Engelman JA. The Allelic Context of the C797S Mutation Acquired upon Treatment with Third-Generation EGFR Inhibitors Impacts Sensitivity to Subsequent Treatment Strategies. Clin Cancer Res 2015; 21:3924-33.
    • KRAS, MET
    • R2 Ortiz-Cuaran S, Scheffler M, Plenker D, Dahmen L, Scheel AH, Fernandez-Cuesta L, Meder L, Lovly CM, Persigehl T, Merkelbach-Bruse S, Bos M, Michels S, Fischer R, Albus K, König K, Schildhaus HU, Fassunke J, Ihle MA, Pasternack H, Heydt C, Becker C, Altmüller J, Ji H, Müller C, Florin A, Heuckmann JM, Nuernberg P, Ansén S, Heukamp LC, Berg J, Pao W, Peifer M, Buettner R, Wolf J, Thomas RK, Sos ML. Heterogeneous Mechanisms of Primary and Acquired Resistance to Third-Generation EGFR Inhibitors. Clin Cancer Res 2016; 22:4837-4847.
    • EGFR, KRAS, PIK3CA
    • R2 Nukaga S, Yasuda H, Tsuchihara K, Hamamoto J, Masuzawa K, Kawada I, Naoki K, Matsumoto S, Mimaki S, Ikemura S, Goto K, Betsuyaku T, Soejima K. Amplification of EGFR Wild-Type Alleles in Non-Small Cell Lung Cancer Cells Confers Acquired Resistance to Mutation-Selective EGFR Tyrosine Kinase Inhibitors. Cancer Res 2017; 77:2078-2089.
    • EGFR
    • R2 Knebel FH, Bettoni F, Shimada AK, Cruz M, Alessi JV, Negrão MV, Reis LFL, Katz A, Camargo AA. Sequential liquid biopsies reveal dynamic alterations of EGFR driver mutations and indicate EGFR amplification as a new mechanism of resistance to osimertinib in NSCLC. Lung Cancer 2017; 108:238-241.
    • R2 Yang Z, Yang N, Ou Q, Xiang Y, Jiang T, Wu X, Bao H, Tong X, Wang X, Shao YW, Liu Y, Wang Y, Zhou C. Investigating Novel Resistance Mechanisms to Third-Generation EGFR Tyrosine Kinase Inhibitor Osimertinib in Non-Small Cell Lung Cancer Patients. Clin Cancer Res 2018; 24:3097-3107.
    • R2 Huang J, Wang Y, Zhai Y, Wang J. Non-small cell lung cancer harboring a rare EGFR L747P mutation showing intrinsic resistance to both gefitinib and osimertinib (AZD9291): A case report. Thorac Cancer 2018; 9:745-749.
    • EGFR+ROS1
    • R2 Zeng L, Yang N, Zhang Y. GOPC-ROS1 Rearrangement as an Acquired Resistance Mechanism to Osimertinib and Responding to Crizotinib Combined Treatments in Lung Adenocarcinoma. J Thorac Oncol 2018; 13:e114-e116.
    • ERBB2
    • R2 Nagano M, Kohsaka S, Ueno T, Kojima S, Saka K, Iwase H, Kawazu M, Mano H. High-Throughput Functional Evaluation of Variants of Unknown Significance in ERBB2. Clin Cancer Res 2018; 24:5112-5122.
    • EGFR
    • R2 Oxnard GR, Hu Y, Mileham KF, Husain H, Costa DB, Tracy P, Feeney N, Sholl LM, Dahlberg SE, Redig AJ, Kwiatkowski DJ, Rabin MS, Paweletz CP, Thress KS, Jänne PA. Assessment of Resistance Mechanisms and Clinical Implications in Patients With EGFR T790M-Positive Lung Cancer and Acquired Resistance to Osimertinib. JAMA Oncol 2018; 4:1527-1534.
    • EGFR+RET
    • R2 Piotrowska Z, Isozaki H, Lennerz JK, Gainor JF, Lennes IT, Zhu VW, Marcoux N, Banwait MK, Digumarthy SR, Su W, Yoda S, Riley AK, Nangia V, Lin JJ, Nagy RJ, Lanman RB, Dias-Santagata D, Mino-Kenudson M, Iafrate AJ, Heist RS, Shaw AT, Evans EK, Clifford C, Ou SI, Wolf B, Hata AN, Sequist LV. Landscape of Acquired Resistance to Osimertinib in EGFR-Mutant NSCLC and Clinical Validation of Combined EGFR and RET Inhibition with Osimertinib and BLU-667 for Acquired RET Fusion. Cancer Discov 2018; 8:1529-1539.
    • EGFR+RB1, EGFR+TP53
    • R2 Marcoux N, Gettinger SN, O'Kane G, Arbour KC, Neal JW, Husain H, Evans TL, Brahmer JR, Muzikansky A, Bonomi PD, Del Prete S, Wurtz A, Farago AF, Dias-Santagata D, Mino-Kenudson M, Reckamp KL, Yu HA, Wakelee HA, Shepherd FA, Piotrowska Z, Sequist LV. EGFR-Mutant Adenocarcinomas That Transform to Small-Cell Lung Cancer and Other Neuroendocrine Carcinomas: Clinical Outcomes. J Clin Oncol 2019; 37:278-285.
    • MET
    • R2 Lai GGY, Lim TH, Lim J, Liew PJR, Kwang XL, Nahar R, Aung ZW, Takano A, Lee YY, Lau DPX, Tan GS, Tan SH, Tan WL, Ang MK, Toh CK, Tan BS, Devanand A, Too CW, Gogna A, Ong BH, Koh TPT, Kanesvaran R, Ng QS, Jain A, Rajasekaran T, Yuan J, Lim TKH, Lim AST, Hillmer AM, Lim WT, Iyer NG, Tam WL, Zhai W, Tan EH, Tan DSW. Clonal MET Amplification as a Determinant of Tyrosine Kinase Inhibitor Resistance in Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer. J Clin Oncol 2019; 37:876-884.
    • EGFR+ALK, EGFR+RET
    • R2 Offin M, Somwar R, Rekhtman N, Benayed R, Chang JC, Plodkowski A, Lui AJW, Eng J, Rosenblum M, Li BT, Riely GJ, Rudin CM, Kris MG, Travis W, Drilon A, Arcila ME, Ladanyi M, Yu HA. Acquired ALK and RET Gene Fusions as Mechanisms of Resistance to Osimertinib in EGFR-Mutant Lung Cancers. JCO Precis Oncol 2018;2.
    • EGFR+EGFR
    • R2 Zhou Z, Zhao Y, Shen S, Gu L, Niu X, Xu Y, Zhang T, Xiang J, Mao X, Lu S. Durable Clinical Response of Lung Adenocarcinoma Harboring EGFR 19Del/T790M/in trans-C797S to Combination Therapy of First- and Third-Generation EGFR Tyrosine Kinase Inhibitors. J Thorac Oncol 2019; 14:e157-e159.
    • EGFR
    • R2 Truini A, Starrett JH, Stewart T, Ashtekar K, Walther Z, Wurtz A, Lu D, Park JH, DeVeaux M, Song X, Gettinger S, Zelterman D, Lemmon MA, Goldberg SB, Politi K. The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma. Clin Cancer Res 2019; 25:6382-6391.
    • R2 Yang Z, Yang J, Chen Y, Shao YW, Wang X. Acquired EGFR L718V Mutation as the Mechanism for Osimertinib Resistance in a T790M-Negative Non-Small-Cell Lung Cancer Patient. Target Oncol 2019; 14:369-374.
    • ERBB2
    • R2 Hsu CC, Liao BC, Liao WY, Markovets A, Stetson D, Thress K, Yang JC. Exon 16-Skipping HER2 as a Novel Mechanism of Osimertinib Resistance in EGFR L858R/T790M-Positive Non-Small Cell Lung Cancer. J Thorac Oncol 2020; 15:50-61.
    • EGFR
    • R2 Zhu C, Zhuang W, Chen L, Yang W, Ou WB. Frontiers of ctDNA, targeted therapies, and immunotherapy in non-small-cell lung cancer. Transl Lung Cancer Res 2020; 9:111-138.
    • R2 Mu Y, Hao X, Xing P, Hu X, Wang Y, Li T, Zhang J, Xu Z, Li J. Acquired resistance to osimertinib in patients with non-small-cell lung cancer: mechanisms and clinical outcomes. J Cancer Res Clin Oncol 2020; 146:2427-2433.
    • ERBB2
    • R2 Yamaoka T, Tsurutani J, Sagara H, Ohmori T. HER2-D16 oncogenic driver mutation confers osimertinib resistance in EGFR mutation-positive non-small cell lung cancer. Transl Lung Cancer Res 2020; 9:2178-2183.
    • EGFR+BRAF
    • R2 Ribeiro MFSA, Knebel FH, Bettoni F, Saddi R, Sacardo KP, Canedo FSNA, Alessi JVM, Shimada AK, Marin JFG, Camargo AA, Katz A. Impressive response to dabrafenib, trametinib, and osimertinib in a metastatic EGFR-mutant/BRAF V600E lung adenocarcinoma patient. NPJ Precis Oncol 2021; 5:5.
    • EGFR
    • R2 Lee C, Kim M, Kim DW, Kim TM, Kim S, Im SW, Jeon YK, Keam B, Ku JL, Heo DS. Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non-Small Cell Lung Cancer. Cancer Res Treat 2021 May 3. [Epub ahead of print]
    • R2 Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 2021; 597:732-737.
    • ERBB2
    • R2 Koga T, Suda K, Nishino M, Fujino T, Ohara S, Hamada A, Soh J, Tirunagaru V, Vellanki A, Doebele RC, Mitsudomi T. Activity and mechanism of acquired resistance to tarloxotinib in HER2 mutant lung cancer: an in vitro study. Transl Lung Cancer Res 2021; 10:3659-3670.
    • EGFR
    • 1 Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med 2017; 376:629-640. <