Genetic Association of Drug Response to Erlotinib in Chinese Advanced Non-small Cell Lung Cancer Patients

Overview

Journal Front Pharmacol

Date 2018 Apr 27

PMID 29695969

Citations 7

Authors

Cong Wang

Fang Chen

Yichen Liu

Qingqing Xu

Liang Guo

Xiaoqing Zhang

Yunfeng Ruan

Ye Shi

Lu Shen

Mo Li

Huihui Du

Xiaofang Sun

Jingsong Ma

Lin He

Shengying Qin

Affiliations

Soon will be listed here.

Abstract

The efficacy of erlotinib treatment for advanced non-small cell lung cancer (NSCLC) is due to its action as an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Patients treated with erlotinib experience different drug responses. The effect of germline mutations on therapeutic responses and adverse drug responses (ADRs) to erlotinib in Chinese patients requires elucidation. Sixty Han Chinese advanced non-small cell lung cancer patients received erlotinib monotherapy and, for each participant, 76 candidate genes (related to EGFR signaling, drug metabolism and drug transport pathways) were sequenced and analyzed. The single-nucleotide polymorphisms (SNPs) rs1042640 in , rs1060463, and rs1064796 in , and rs2074900 in were significantly associated with therapeutic responses to erlotinib. Rs1064796 in and rs10045685 in were significantly associated with adverse drug reaction. Moreover, analysis of a validation cohort confirmed the significant association between rs10045685 in and erlotinib adverse drug response(unadjusted = 0.015). This study provides comprehensive, systematic analyses of genetic variants associated with responses to erlotinib in Chinese advanced non-small cell lung cancer patients. Newly-identified SNPs may serve as promising markers to predict responses and safety in erlotinib-treated advanced non-small cell lung cancer patients after chemotherapy doublet.

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References

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136(5):E359-86. DOI: 10.1002/ijc.29210. View

Hirsch F, Kabbinavar F, Eisen T, Martins R, Schnell F, Dziadziuszko R . A randomized, phase II, biomarker-selected study comparing erlotinib to erlotinib intercalated with chemotherapy in first-line therapy for advanced non-small-cell lung cancer. J Clin Oncol. 2011; 29(26):3567-73. PMC: 3179254. DOI: 10.1200/JCO.2010.34.4929. View

Ruan Y, Jiang J, Guo L, Li Y, Huang H, Shen L . Genetic Association of Curative and Adverse Reactions to Tyrosine Kinase Inhibitors in Chinese advanced Non-Small Cell Lung Cancer patients. Sci Rep. 2016; 6:23368. PMC: 4796893. DOI: 10.1038/srep23368. View

Lopez-Ayllon B, de Castro-Carpeno J, Rodriguez C, Pernia O, de Caceres I, Belda-Iniesta C . Biomarkers of erlotinib response in non-small cell lung cancer tumors that do not harbor the more common epidermal growth factor receptor mutations. Int J Clin Exp Pathol. 2015; 8(3):2888-98. PMC: 4440106. View

Bardelli A, Parsons D, Silliman N, Ptak J, Szabo S, Saha S . Mutational analysis of the tyrosine kinome in colorectal cancers. Science. 2003; 300(5621):949. DOI: 10.1126/science.1082596. View

Lu L, Zhou J, Shi J, Peng X, Qi X, Wang Y . Drug-Metabolizing Activity, Protein and Gene Expression of UDP-Glucuronosyltransferases Are Significantly Altered in Hepatocellular Carcinoma Patients. PLoS One. 2015; 10(5):e0127524. PMC: 4444081. DOI: 10.1371/journal.pone.0127524. View

Florescu M, Hasan B, Seymour L, Ding K, Shepherd F . A clinical prognostic index for patients treated with erlotinib in National Cancer Institute of Canada Clinical Trials Group study BR.21. J Thorac Oncol. 2008; 3(6):590-8. DOI: 10.1097/JTO.0b013e3181729299. View

Wang Y, Bell J, Keeney D, Strobel H . Gene regulation of CYP4F11 in human keratinocyte HaCaT cells. Drug Metab Dispos. 2009; 38(1):100-7. PMC: 2802424. DOI: 10.1124/dmd.109.029025. View

Kim W, Lee J, Yi J, Cho Y, Heo K, Lee S . A nonsynonymous variation in MRP2/ABCC2 is associated with neurological adverse drug reactions of carbamazepine in patients with epilepsy. Pharmacogenet Genomics. 2010; 20(4):249-56. DOI: 10.1097/FPC.0b013e328338073a. View

10.

Sawyers C . Opportunities and challenges in the development of kinase inhibitor therapy for cancer. Genes Dev. 2004; 17(24):2998-3010. DOI: 10.1101/gad.1152403. View

11.

Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S . RET, ROS1 and ALK fusions in lung cancer. Nat Med. 2012; 18(3):378-81. DOI: 10.1038/nm.2658. View

12.

Greenhalgh J, Bagust A, Boland A, Dwan K, Beale S, Hockenhull J . Erlotinib and gefitinib for treating non-small cell lung cancer that has progressed following prior chemotherapy (review of NICE technology appraisals 162 and 175): a systematic review and economic evaluation. Health Technol Assess. 2015; 19(47):1-134. PMC: 4781386. DOI: 10.3310/hta19470. View

13.

Xiao X, Xia S, Zou M, Mei Q, Zhou L, Wang S . The relationship between UGT1A1 gene polymorphism and irinotecan effect on extensive-stage small-cell lung cancer. Onco Targets Ther. 2015; 8:3575-83. PMC: 4671801. DOI: 10.2147/OTT.S95149. View

14.

McKillop D, Guy S, SPENCE M, Kendrew J, Kemp J, Bushby N . Minimal contribution of desmethyl-gefitinib, the major human plasma metabolite of gefitinib, to epidermal growth factor receptor (EGFR)-mediated tumour growth inhibition. Xenobiotica. 2006; 36(1):29-39. DOI: 10.1080/00498250500523253. View

15.

Gurley B, Swain A, Hubbard M, Williams D, Barone G, Hartsfield F . Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Mol Nutr Food Res. 2008; 52(7):755-63. PMC: 2562884. DOI: 10.1002/mnfr.200600300. View

16.

Schmid S, Gautschi O, Rothschild S, Mark M, Froesch P, Klingbiel D . Clinical Outcome of ALK-Positive Non-Small Cell Lung Cancer (NSCLC) Patients with De Novo EGFR or KRAS Co-Mutations Receiving Tyrosine Kinase Inhibitors (TKIs). J Thorac Oncol. 2016; 12(4):681-688. DOI: 10.1016/j.jtho.2016.12.003. View

17.

Riely G, Marks J, Pao W . KRAS mutations in non-small cell lung cancer. Proc Am Thorac Soc. 2009; 6(2):201-5. DOI: 10.1513/pats.200809-107LC. View

18.

Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E . Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012; 13(3):239-46. DOI: 10.1016/S1470-2045(11)70393-X. View

19.

Yang N, Sun R, Liao X, Aa J, Wang G . UDP-glucuronosyltransferases (UGTs) and their related metabolic cross-talk with internal homeostasis: A systematic review of UGT isoforms for precision medicine. Pharmacol Res. 2017; 121:169-183. DOI: 10.1016/j.phrs.2017.05.001. View

20.

Suzumura T, Kimura T, Kudoh S, Umekawa K, Nagata M, Matsuura K . Reduced CYP2D6 function is associated with gefitinib-induced rash in patients with non-small cell lung cancer. BMC Cancer. 2012; 12:568. PMC: 3536666. DOI: 10.1186/1471-2407-12-568. View