Mechanisms of resistance to third-generation EGFR tyrosine kinase inhibitors

doi:10.1007/s11684-016-0488-1

Front. Med.

2016, Vol. 10

Issue (4) : 383-388 https://doi.org/10.1007/s11684-016-0488-1

REVIEW

Mechanisms of resistance to third-generation EGFR tyrosine kinase inhibitors

Shuhang Wang¹,Yongping Song²,Feifei Yan¹,Delong Liu²(

)

¹. The Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital, Beijing 100142, China
². Henan Cancer Hospital and the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China

Download: PDF(121 KB) HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Abstract

The tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) are becoming the first line of therapy for advanced non-small cell lung cancer (NSCLC). Acquired mutations in EGFR account for one of the major mechanisms of resistance to the TKIs. Three generations of EGFR TKIs have been used in clinical applications. AZD9291 (osimertinib; Tagrisso) is the first and only FDA approved third-generation EGFR TKI for T790M-positive advanced NSCLC patients. However, resistance to AZD9291 arises after 9–13 months of therapy. The mechanisms of resistance to third-generation inhibitors reported to date include the EGFR C797S mutation, EGFR L718Q mutation, and amplifications of HER-2, MET, or ERBB2. To overcome the acquired resistance to AZD9291, EAI045 was discovered and recently reported to be an allosteric EGFR inhibitor that overcomes T790M- and C797S-mediated resistance. This review summarizes recent investigations on the mechanisms of resistance to the EGFR TKIs, as well as the latest development of EAI045 as a fourth-generation EGFR inhibitor.

Keywords EGFR tyrosine kinase inhibitor AZD9291 EAI045

Corresponding Author(s): Delong Liu

Just Accepted Date: 08 October 2016 Online First Date: 24 October 2016 Issue Date: 01 December 2016

Cite this article:

Shuhang Wang,Yongping Song,Feifei Yan, et al. Mechanisms of resistance to third-generation EGFR tyrosine kinase inhibitors[J]. Front. Med., 2016, 10(4): 383-388.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-016-0488-1
https://academic.hep.com.cn/fmd/EN/Y2016/V10/I4/383

Tab.1 Patients with NSCLC who developed resistance to third-generation EGFR TKIs

1	Iragavarapu C, Mustafa M, Akinleye A, Furqan M, Mittal V, Cang S, Liu D. Novel ALK inhibitors in clinical use and development. J Hematol Oncol 2015; 8(1): 17 https://doi.org/10.1186/s13045-015-0122-8 pmid: 25888090
2	Wang S, Cang S, Liu D. Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer. J Hematol Oncol 2016; 9(1): 34 https://doi.org/10.1186/s13045-016-0268-z pmid: 27071706
3	West H. Nivolumab as first line monotherapy for advanced non-small cell lung cancer: could we replace first line chemotherapy with immunotherapy? Transl Lung Cancer Res 2014; 3(6): 400–402 pmid: 25806333
4	Wu J, Savooji J, Liu D. Second- and third-generation ALK inhibitors for non-small cell lung cancer. J Hematol Oncol 2016; 9(1): 19 https://doi.org/10.1186/s13045-016-0251-8 pmid: 26951079
5	Zhou W, Ercan D, Chen L, Yun CH, Li D, Capelletti M, Cortot AB, Chirieac L, Iacob RE, Padera R, Engen JR, Wong KK, Eck MJ, Gray NS, Jänne PA. Novel mutant-selective EGFR kinase inhibitors against EGFR T790M. Nature 2009; 462(7276): 1070–1074 https://doi.org/10.1038/nature08622 pmid: 20033049
6	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(5): 577–589 https://doi.org/10.1016/S1470-2045(16)30033-X pmid: 27083334
7	Chi A, Remick S, Tse W. EGFR inhibition in non-small cell lung cancer: current evidence and future directions. Biomark Res 2013; 1(1): 2 https://doi.org/10.1186/2050-7771-1-2 pmid: 24252457
8	Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, Lu S, Cheng Y, Han B, Chen L, Huang C, Qin S, Zhu Y, Pan H, Liang H, Li E, Jiang G, How SH, Fernando MC, Zhang Y, Xia F, Zuo Y. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol 2015; 26(9): 1883–1889 https://doi.org/10.1093/annonc/mdv270 pmid: 26105600
9	Soria JC, Wu YL, Nakagawa K, Kim SW, Yang JJ, Ahn MJ, Wang J, Yang JC, Lu Y, Atagi S, Ponce S, Lee DH, Liu Y, Yoh K, Zhou JY, Shi X, Webster A, Jiang H, Mok TS. Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial. Lancet Oncol 2015; 16(8): 990–998 https://doi.org/10.1016/S1470-2045(15)00121-7 pmid: 26159065
10	Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O’Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 2015; 16(2): 141–151 https://doi.org/10.1016/S1470-2045(14)71173-8 pmid: 25589191
11	Zhai H, Zhong W, Yang X, Wu YL. Neoadjuvant and adjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy for lung cancer. Transl Lung Cancer Res 2015; 4(1): 82–93 pmid: 25806348
12	Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol 2015; 26(9): 1877–1883 https://doi.org/10.1093/annonc/mdv276 pmid: 26141208
13	Soria JC, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Li W, Isla D, Guclu SZ, Morabito A, Min YJ, Ardizzoni A, Gadgeel SM, Wang B, Chand VK, Goss GD; LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol 2015; 16(8): 897–907 https://doi.org/10.1016/S1470-2045(15)00006-6 pmid: 26156651
14	Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007; 7(3): 169–181 https://doi.org/10.1038/nrc2088 pmid: 17318210
15	Niu FY, Wu YL. Novel agents and strategies for overcoming EGFR TKIs resistance. Exp Hematol Oncol 2014; 3(1): 2 https://doi.org/10.1186/2162-3619-3-2 pmid: 24410791
16	Engel J, Richters A, Getlik M, Tomassi S, Keul M, Termathe M, Lategahn J, Becker C, Mayer-Wrangowski S, Grütter C, Uhlenbrock N, Krüll J, Schaumann N, Eppmann S, Kibies P, Hoffgaard F, Heil J, Menninger S, Ortiz-Cuaran S, Heuckmann JM, Tinnefeld V, Zahedi RP, Sos ML, Schultz-Fademrecht C, Thomas RK, Kast SM, Rauh D. Targeting drug resistance in EGFR with covalent inhibitors: a structure-based design approach. J Med Chem 2015; 58(17): 6844–6863 https://doi.org/10.1021/acs.jmedchem.5b01082 pmid: 26275028
17	Cross DA, Ashton SE, Ghiorghiu S, Eberlein C, Nebhan CA, Spitzler PJ, Orme JP, Finlay MR, Ward RA, Mellor MJ, Hughes G, Rahi A, Jacobs VN, Red Brewer M, Ichihara E, Sun J, Jin H, Ballard P, Al-Kadhimi K, Rowlinson R, Klinowska T, Richmond GH, Cantarini M, Kim DW, Ranson MR, Pao W. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov 2014; 4(9): 1046–1061 https://doi.org/10.1158/2159-8290.CD-14-0337 pmid: 24893891
18	Park KLJS, Lee KH, Kim JH, Min YJ, Cho JY, Han JY, Kim BS, Kim JS, Lee DH, Kang JH, Cho EK, Jang IJ. Jung J, Kim H-Y, Sin HJ, Son J, Woo JS, Kim D-W. Updated safety and efficacy results from phase I/II study of HM61713 in patients (pts) with EGFR mutation positive non-small cell lung cancer (NSCLC) who failed previous EGFR-tyrosine kinase inhibitor (TKI). ASCO Meeting Abstracts 2015;33(15_suppl):8084
19	Sequist LV, Rolfe L, Allen AR. Rociletinib in EGFR-mutated non-small-cell lung cancer. N Engl J Med 2015; 373(6): 578–579 https://doi.org/10.1056/NEJMc1506831 pmid: 26244318
20	Walter AO, Sjin RT, Haringsma HJ, Ohashi K, Sun J, Lee K, Dubrovskiy A, Labenski M, Zhu Z, Wang Z, Sheets M, St Martin T, Karp R, van Kalken D, Chaturvedi P, Niu D, Nacht M, Petter RC, Westlin W, Lin K, Jaw-Tsai S, Raponi M, Van Dyke T, Etter J, Weaver Z, Pao W, Singh J, Simmons AD, Harding TC, Allen A. Discovery of a mutant-selective covalent inhibitor of EGFR that overcomes T790M-mediated resistance in NSCLC. Cancer Discov 2013; 3(12): 1404–1415 https://doi.org/10.1158/2159-8290.CD-13-0314 pmid: 24065731
21	Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, Padera RF, Shapiro GI, Baum A, Himmelsbach F, Rettig WJ, Meyerson M, Solca F, Greulich H, Wong KK. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 2008; 27(34): 4702–4711 https://doi.org/10.1038/onc.2008.109 pmid: 18408761
22	Planchard D, Loriot Y, André F, Gobert A, Auger N, Lacroix L, Soria JC. EGFR-independent mechanisms of acquired resistance to AZD9291 in EGFR T790M-positive NSCLC patients. Ann Oncol 2015; 26(10): 2073–2078 https://doi.org/10.1093/annonc/mdv319 pmid: 26269204
23	Thress KS, Paweletz CP, Felip E, Cho BC, Stetson D, Dougherty B, Lai Z, Markovets A, Vivancos A, Kuang Y, Ercan D, Matthews SE, Cantarini M, Barrett JC, Jänne PA, Oxnard GR. Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat Med 2015; 21(6): 560–562 https://doi.org/10.1038/nm.3854 pmid: 25939061
24	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(17): 3924–3933 https://doi.org/10.1158/1078-0432.CCR-15-0560 pmid: 25964297
25	Yu HA, Tian SK, Drilon AE, Borsu L, Riely GJ, Arcila ME, Ladanyi M. Acquired resistance of EGFR-mutant lung cancer to a T790M-specific EGFR inhibitor: emergence of a third mutation (C797S) in the EGFR tyrosine kinase domain. JAMA Oncol 2015; 1(7): 982–984 https://doi.org/10.1001/jamaoncol.2015.1066 pmid: 26181354
26	Wang S, Tsui ST, Liu C, Song Y, Liu D. EGFR C797S mutation mediates resistance to third-generation inhibitors in T790M-positive non-small cell lung cancer. J Hematol Oncol 2016; 9(1): 59 https://doi.org/10.1186/s13045-016-0290-1 pmid: 27448564
27	Song HN, Jung KS, Yoo KH, Cho J, Lee JY, Lim SH, Kim HS, Sun JM, Lee SH, Ahn JS, Park K, Choi YL, Park W, Ahn MJ. Acquired C797S mutation upon treatment with a T790M-specific third-generation EGFR inhibitor (HM61713) in non-small cell lung cancer. J Thorac Oncol 2016; 11(4): e45–e47 https://doi.org/10.1016/j.jtho.2015.12.093 pmid: 26749488
28	Ercan D, Choi HG, Yun CH, Capelletti M, Xie T, Eck MJ, Gray NS, Jänne PA. EGFR mutations and resistance to irreversible pyrimidine-based EGFR inhibitors. Clin Cancer Res 2015; 21(17): 3913–3923 https://doi.org/10.1158/1078-0432.CCR-14-2789 pmid: 25948633
29	Bersanelli M, Minari R, Bordi P, Gnetti L, Bozzetti C, Squadrilli A, Lagrasta CA, Bottarelli L, Osipova G, Capelletto E, Mor M, Tiseo M. L718Q mutation as new mechanism of acquired resistance to AZD9291 in EGFR-mutated NSCLC. J Thorac Oncol 2016; 11(10):e121–123 https://doi.org/10.1016/j.jtho.2016.1005.1019 pmid: 27257132
30	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(19):4837-4847 https://doi.org/10.1158/1078-0432.CCR-1115-1915 pmid: 27252416
31	Jia Y, Yun CH, Park E, Ercan D, Manuia M, Juarez J, Xu C, Rhee K, Chen T, Zhang H, Palakurthi S, Jang J, Lelais G, DiDonato M, Bursulaya B, Michellys PY, Epple R, Marsilje TH, McNeill M, Lu W, Harris J, Bender S, Wong KK, Jänne PA, Eck MJ. Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors. Nature 2016; 534(7605): 129–132 https://doi.org/10.1038/nature17960 pmid: 27251290
32	Brevet M, Johnson ML, Azzoli CG, Ladanyi M. Detection of EGFR mutations in plasma DNA from lung cancer patients by mass spectrometry genotyping is predictive of tumor EGFR status and response to EGFR inhibitors. Lung Cancer 2011; 73(1): 96–102 https://doi.org/10.1016/j.lungcan.2010.10.014 pmid: 21130517
33	Luo J, Shen L, Zheng D. Diagnostic value of circulating free DNA for the detection of EGFR mutation status in NSCLC: a systematic review and meta-analysis. Sci Rep 2014; 4: 6269 https://doi.org/10.1038/srep06269 pmid: 25201768
34	Ma M, Shi C, Qian J, Teng J, Zhong H, Han B. Comparison of plasma and tissue samples in epidermal growth factor receptor mutation by ARMS in advanced non-small cell lung cancer. Gene 2016; 591(1): 58–64 https://doi.org/10.1016/j.gene.2016.06.053 pmid: 27370697
35	Matikas A, Syrigos KN, Agelaki S. Circulating biomarkers in non-small-cell lung cancer: current status and future challenges. Clin Lung Cancer 2016 Jun 8. [Epub ahead of print] doi:10.1016/j.cllc.2016.1005.1021 https://doi.org/10.1016/j.cllc.2016.1005.1021PMID:27373516
36	Sun W, Yuan X, Tian Y, Wu H, Xu H, Hu G, Wu K. Non-invasive approaches to monitor EGFR-TKI treatment in non-small-cell lung cancer. J Hematol Oncol 2015; 8(1): 95 https://doi.org/10.1186/s13045-015-0193-6 pmid: 26227959
37	Wu Y, Liu H, Shi X, Song Y. Can EGFR mutations in plasma or serum be predictive markers of non-small-cell lung cancer? A meta-analysis. Lung Cancer 2015; 88(3): 246–253 https://doi.org/10.1016/j.lungcan.2015.03.008 pmid: 25837799
38	Cang S, Iragavarapu C, Savooji J, Song Y, Liu D. ABT-199 (venetoclax) and BCL-2 inhibitors in clinical development. J Hematol Oncol 2015; 8(1): 129 https://doi.org/10.1186/s13045-015-0224-3 pmid: 26589495
39	Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, Bruncko M, Deckwerth TL, Dinges J, Hajduk PJ, Joseph MK, Kitada S, Korsmeyer SJ, Kunzer AR, Letai A, Li C, Mitten MJ, Nettesheim DG, Ng S, Nimmer PM, O’Connor JM, Oleksijew A, Petros AM, Reed JC, Shen W, Tahir SK, Thompson CB, Tomaselli KJ, Wang B, Wendt MD, Zhang H, Fesik SW, Rosenberg SH. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 2005; 435(7042): 677–681 https://doi.org/10.1038/nature03579 pmid: 15902208
40	Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, Dayton BD, Ding H, Enschede SH, Fairbrother WJ, Huang DC, Hymowitz SG, Jin S, Khaw SL, Kovar PJ, Lam LT, Lee J, Maecker HL, Marsh KC, Mason KD, Mitten MJ, Nimmer PM, Oleksijew A, Park CH, Park CM, Phillips DC, Roberts AW, Sampath D, Seymour JF, Smith ML, Sullivan GM, Tahir SK, Tse C, Wendt MD, Xiao Y, Xue JC, Zhang H, Humerickhouse RA, Rosenberg SH, Elmore SW. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med 2013; 19(2): 202–208 https://doi.org/10.1038/nm.3048 pmid: 23291630
41	Tsujimoto Y, Shimizu S. Bcl-2 family: life-or-death switch. FEBS Lett 2000; 466(1): 6–10 https://doi.org/10.1016/S0014-5793(99)01761-5 pmid: 10648802
42	Das A, Wei G, Parikh K, Liu D. Selective inhibitors of nuclear export (SINE) in hematological malignancies. Exp Hematol Oncol 2015; 4(1): 7 https://doi.org/10.1186/s40164-015-0002-5 pmid: 25745591
43	Gravina GL, Senapedis W, McCauley D, Baloglu E, Shacham S, Festuccia C. Nucleo-cytoplasmic transport as a therapeutic target of cancer. J Hematol Oncol 2014; 7(1): 85 https://doi.org/10.1186/s13045-014-0085-1 pmid: 25476752
44	Gravina GL, Tortoreto M, Mancini A, Addis A, Di Cesare E, Lenzi A, Landesman Y, McCauley D, Kauffman M, Shacham S, Zaffaroni N, Festuccia C. XPO1/CRM1-selective inhibitors of nuclear export (SINE) reduce tumor spreading and improve overall survival in preclinical models of prostate cancer (PCa). J Hematol Oncol 2014; 7(1): 46 https://doi.org/10.1186/1756-8722-7-46 pmid: 25284315
45	Parikh K, Cang S, Sekhri A, Liu D. Selective inhibitors of nuclear export (SINE)—a novel class of anti-cancer agents. J Hematol Oncol 2014; 7(1): 78 https://doi.org/10.1186/s13045-014-0078-0 pmid: 25316614
46	Naidu S, Magee P, Garofalo M. miRNA-based therapeutic intervention of cancer. J Hematol Oncol 2015; 8(1): 68 https://doi.org/10.1186/s13045-015-0162-0 pmid: 26062952
47	Sanchez-Mejias A, Tay Y. Competing endogenous RNA networks: tying the essential knots for cancer biology and therapeutics. J Hematol Oncol 2015; 8(1): 30 https://doi.org/10.1186/s13045-015-0129-1 pmid: 25888444
48	Alexander PB, Wang XF. Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies. Front Med 2015; 9(2): 134–138 https://doi.org/10.1007/s11684-015-0396-9 pmid: 25957263
49	Cho J, Chen L, Sangji N, Okabe T, Yonesaka K, Francis JM, Flavin RJ, Johnson W, Kwon J, Yu S, Greulich H, Johnson BE, Eck MJ, Jänne PA, Wong KK, Meyerson M. Cetuximab response of lung cancer-derived EGF receptor mutants is associated with asymmetric dimerization. Cancer Res 2013; 73(22): 6770–6779 https://doi.org/10.1158/0008-5472.CAN-13-1145 pmid: 24063894
50	Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Arén Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus docetaxel in advanced squamous-cell non-amall-cell lung cancer. N Engl J Med 2015; 373(2): 123–135 https://doi.org/10.1056/NEJMoa1504627 pmid: 26028407
51	Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhäufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crinò L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015; 373(17): 1627–1639 https://doi.org/10.1056/NEJMoa1507643 pmid: 26412456
52	Davar D, Socinski MA, Dacic S, Burns TF. Near complete response after single dose of nivolumab in patient with advanced heavily pre-treated KRAS mutant pulmonary adenocarcinoma. Exp Hematol Oncol 2015; 4(1): 34 https://doi.org/10.1186/s40164-015-0029-7 pmid: 26673119
53	Schuller AG, Barry ER, Jones RD, Henry RE, Frigault MM, Beran G, Linsenmayer D, Hattersley M, Smith A, Wilson J, Cairo S, Déas O, Nicolle D, Adam A, Zinda M, Reimer C, Fawell SE, Clark EA, D’Cruz CM. The MET inhibitor AZD6094 (savolitinib, HMPL-504) induces regression in papillary renal cell carcinoma patient-derived xenograft models. Clin Cancer Res 2015; 21(12): 2811–2819 https://doi.org/10.1158/1078-0432.CCR-14-2685 pmid: 25779944
54	Ho AL, Grewal RK, Leboeuf R, Sherman EJ, Pfister DG, Deandreis D, Pentlow KS, Zanzonico PB, Haque S, Gavane S, Ghossein RA, Ricarte-Filho JC, Domínguez JM, Shen R, Tuttle RM, Larson SM, Fagin JA. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. N Engl J Med 2013; 368(7): 623–632 https://doi.org/10.1056/NEJMoa1209288 pmid: 23406027
55	Smith AD, Roda D, Yap TA. Strategies for modern biomarker and drug development in oncology. J Hematol Oncol 2014; 7(1): 70 https://doi.org/10.1186/s13045-014-0070-8 pmid: 25277503
56	Zhong W, Yang X, Yan H, Zhang X, Su J, Chen Z, Liao R, Nie Q, Dong S, Zhou Q, Yang J, Tu H, Wu YL. Phase II study of biomarker-guided neoadjuvant treatment strategy for IIIA-N2 non-small cell lung cancer based on epidermal growth factor receptor mutation status. J Hematol Oncol 2015; 8(1): 54 https://doi.org/10.1186/s13045-015-0151-3 pmid: 25981169
57	Lindeman NI, Cagle PT, Beasley MB, Chitale DA, Dacic S, Giaccone G, Jenkins RB, Kwiatkowski DJ, Saldivar JS, Squire J, Thunnissen E, Ladanyi M. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Thorac Oncol 2013; 8(7): 823–859 https://doi.org/10.1097/JTO.0b013e318290868f pmid: 23552377
58	Sun Z, Chen X, Wang G, Li L, Fu G, Kuruc M, Wang X. Identification of functional metabolic biomarkers from lung cancer patient serum using PEP technology. Biomark Res 2016; 4(1): 11 https://doi.org/10.1186/s40364-016-0065-4 pmid: 27252855

[1]	Ching-Hon Pui. Precision medicine in acute lymphoblastic leukemia[J]. Front. Med., 2020, 14(6): 689-700.
[2]	Amy Lee, Fa-Chyi Lee. Medical oncology management of advanced hepatocellular carcinoma 2019: a reality check[J]. Front. Med., 2020, 14(3): 273-283.
[3]	Zhen Wang, Jianhui Wu, Xiuyun Tian, Chunyi Hao. Targeted therapy of desmoid-type fibromatosis: mechanism, current situation, and future prospects[J]. Front. Med., 2019, 13(4): 427-437.
[4]	Xiaojun Huang, Qian Jiang, Jianda Hu, Jianyong Li, Jie Jin, Fanyi Meng, Zhixiang Shen, Ting Liu, Depei Wu, Jianmin Wang, Jianxiang Wang. Four-year follow-up of patients with imatinib-resistant or intolerant chronic myeloid leukemia receiving dasatinib: efficacy and safety[J]. Front. Med., 2019, 13(3): 344-353.
[5]	Qiongna Dong, Bizhi Shi, Min Zhou, Huiping Gao, Xiaoying Luo, Zonghai Li, Hua Jiang. Growth suppression of colorectal cancer expressing S492R EGFR by monoclonal antibody CH12[J]. Front. Med., 2019, 13(1): 83-93.

Viewed

Full text

Abstract

Cited

Shared

Discussed