Mechanisms of Acquired Resistance to AZD9291: A Mutation-Selective, Irreversible EGFR Inhibitor

Journal of Thoracic Oncology

Volumn 10, Issue 12, 2015, Pages 1736-1744

  Kim, Tae Min ^a,b   Song, Ahnah ^b   Kim, Dong Wan ^a,b   Kim, Soyeon ^b   Ahn, Yong Oon ^b   Keam, Bhumsuk ^a,b   Jeon, Yoon Kyung ^a   Lee, Se Hoon ^a,b   Chung, Doo Hyun ^a   Heo, Dae Seog ^a,b  

^a Seoul National University Hospital   (South Korea)

^b Seoul National University   (South Korea)

Author keywords

Acquired resistance; AZD9291; Epidermal growth factor receptor T790M mutation; Non small cell lung cancer

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERLOTINIB; FIBROBLAST GROWTH FACTOR 2; FIBROBLAST GROWTH FACTOR RECEPTOR 1; GEFITINIB; MITOGEN ACTIVATED PROTEIN KINASE 1; OSIMERTINIB; PACLITAXEL; PEMETREXED; PROTEIN KINASE B; ACRYLAMIDE DERIVATIVE; ANILINE DERIVATIVE; EGFR PROTEIN, HUMAN; PROTEIN KINASE INHIBITOR;

ADULT; ARTICLE; CANCER RADIOTHERAPY; CANCER RESISTANCE; CANCER THERAPY; CASE REPORT; CLINICAL EVALUATION; COPY NUMBER VARIATION; DNA SEQUENCE; DRUG DOSE ESCALATION; DRUG MECHANISM; EPITHELIAL MESENCHYMAL TRANSITION; FEMALE; FLUORESCENCE IN SITU HYBRIDIZATION; GENE AMPLIFICATION; GENE DELETION; GENE MUTATION; GENE OVEREXPRESSION; HISTOPATHOLOGY; HUMAN; MALE; MIDDLE AGED; MULTIPLE CYCLE TREATMENT; NON SMALL CELL LUNG CANCER; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; REAL TIME POLYMERASE CHAIN REACTION; SMALL CELL CARCINOMA; TREATMENT RESPONSE; ANTAGONISTS AND INHIBITORS; CARCINOMA, NON-SMALL-CELL LUNG; DRUG RESISTANCE; ENZYMOLOGY; GENETICS; LUNG NEOPLASMS; MUTATION; PATHOLOGY; PHASE 1 CLINICAL TRIAL (TOPIC); TREATMENT OUTCOME;

ACRYLAMIDES; ANILINE COMPOUNDS; CARCINOMA, NON-SMALL-CELL LUNG; CLINICAL TRIALS, PHASE I AS TOPIC; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; LUNG NEOPLASMS; MALE; MIDDLE AGED; MUTATION; PROTEIN KINASE INHIBITORS; RECEPTOR, EPIDERMAL GROWTH FACTOR; TREATMENT OUTCOME;

EID: 84948071403     PISSN: 15560864     EISSN: 15561380     Source Type: Journal    
DOI: 10.1097/JTO.0000000000000688     Document Type: Article

References (37)

1. Sordella R, Bell DW, Haber DA, Settleman J. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 2004;305:1163-1167.
2. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129-2139.
3. Paez JG, Jänne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304:1497-1500.
4. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361:947-957.
5. Chong CR, Jänne PA. The quest to overcome resistance to EGFR-targeted therapies in cancer. Nat Med 2013;19:1389-1400.
6. Kobayashi S, Boggon TJ, Dayaram T, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 2005;352:786-792.
7. Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007;316:1039-1043.
8. Takezawa K, Pirazzoli V, Arcila ME, et al. HER2 amplification: a potential mechanism of acquired resistance to EGFR inhibition in EGFRmutant lung cancers that lack the second-site EGFRT790M mutation. Cancer Discov 2012;2:922-933.
9. Ercan D, Xu C, Yanagita M, et al. Reactivation of ERK signaling causes resistance to EGFR kinase inhibitors. Cancer Discov 2012;2:934-947.
10. Sequist LV, Waltman BA, Dias-Santagata D, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 2011;3:75-26.
11. Zhang Z, Lee JC, Lin L, et al. Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat Genet 2012;44:852-860.
12. Yu HA, Arcila ME, Rekhtman N, et al. 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;19:2240-2247.
13. Yun CH, Mengwasser KE, Toms AV, et al. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci USA 2008;105:2070-2075.
14. Engelman JA, Zejnullahu K, Gale CM, et al. PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib. Cancer Res 2007;67:11924-11932.
15. Katakami N, Atagi S, Goto K, et al. LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol 2013;31:3335-3341.
16. Janjigian YY, Smit EF, Groen HJ, et al. Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov 2014;4:1036-1045.
17. Walter AO, Sjin RT, Haringsma HJ, et al. Discovery of a mutant-selective covalent inhibitor of EGFR that overcomes T790M-mediated resistance in NSCLC. Cancer Discov 2013;3:1404-1415.
18. Cross DA, Ashton SE, Ghiorghiu S, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov 2014;4:1046-1061.
19. Jänne PA, Yang JC, Kim DW, et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med 2015;372:1689-1699.
20. Thress KS, Paweletz CP, Felip E, et al. Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat Med 2015;21:560-562.
21. Shien K, Toyooka S, Yamamoto H, et al. Acquired resistance to EGFR inhibitors is associated with a manifestation of stem cell-like properties in cancer cells. Cancer Res 2013;73:3051-3061.
22. Paila U, Chapman BA, Kirchner R, Quinlan AR. GEMINI: integrative exploration of genetic variation and genome annotations. PLoS Comput Biol 2013;9:e1003153.
23. Sequist LV, Soria JC, Goldman JW, et al. Rociletinib in EGFR-mutated non-small-cell lung cancer. N Engl J Med 2015;372:1700-1709.
24. Eberlein CA, Stetson D, Markovets AA, et al. Acquired resistance to the mutant-selective EGFR inhibitor AZD9291 is associated with increased dependence on RAS signaling in preclinical models. Cancer Res 2015;75:2489-2500.
25. Piotrowska Z, Niederst MJ, Karlovich CA, et al. Heterogeneity underlies the emergence of EGFRT790 wild-type clones following treatment of T790M-positive cancers with a third-generation EGFR inhibitor. Cancer Discov 2015;5:713-722.
26. Chmielecki J, Foo J, Oxnard GR, et al. Optimization of dosing for EGFRmutant non-small cell lung cancer with evolutionary cancer modeling. Sci Transl Med 2011;3:90ra59.
27. Doebele RC, Pilling AB, Aisner DL, et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res 2012;18:1472-1482.
28. Tabara K, Kanda R, Sonoda K, et al. Loss of activating EGFR mutant gene contributes to acquired resistance to EGFR tyrosine kinase inhibitors in lung cancer cells. PLoS One 2012;7:e41017.
29. Regales L, Gong Y, Shen R, et al. Dual targeting of EGFR can overcome a major drug resistance mutation in mouse models of EGFR mutant lung cancer. J Clin Invest 2009;119:3000-3010.
30. Bivona TG, Hieronymus H, Parker J, et al. FAS and NF-B signalling modulate dependence of lung cancers on mutant EGFR. Nature 2011;471:523-526.
31. Blakely CM, Pazarentzos E, Olivas V, et al. NF-B-activating complex engaged in response to EGFR oncogene inhibition drives tumor cell survival and residual disease in lung cancer. Cell Rep 2015;11:98-110.
32. Weiss J, Sos ML, Seidel D, et al. Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med 2010;2:62ra93.
33. Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature 2014;511:543-550.
34. Ware KE, Hinz TK, Kleczko E, et al. A mechanism of resistance to gefitinib mediated by cellular reprogramming and the acquisition of an FGF2-FGFR1 autocrine growth loop. Oncogenesis 2013;2:e39.
35. Wilson TR, Fridlyand J, Yan Y, et al. Widespread potential for growthfactor-driven resistance to anticancer kinase inhibitors. Nature 2012;487:505-509.
36. Sos ML, Koker M, Weir BA, et al. PTEN loss contributes to erlotinib resistance in EGFR-mutant lung cancer by activation of Akt and EGFR. Cancer Res 2009;69:3256-3261.
37. Niederst MJ, Sequist LV, Poirier JT, et al. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat Commun 2015;6:6377.