代谢酶及转运体基因多态性对厄洛替尼与吉非替尼治疗效果及毒副反应影响的研究进展  

Impact of genetic polymorphism of drug-metabolizing enzymes and transporters on erlotinib and gefitinib induced treatment responses and adverse events

作　　者：廖德华[1] 符一岚[1] 姚敦武[1] 曹丽芝[1] 李程[2] LIAO De-hua;FU Yi-lan;YAO Dun-wu;CAO Li-zhi;LI Cheng(Department of Pharmacy,Hunan Cancer Hospital,Changsha 410013;School of Medicine,Hunan Normal University,Changsha 410013)

机构地区：[1]湖南省肿瘤医院药学部,长沙410013 [2]湖南师范大学医学院,长沙410013

出　　处：《中南药学》2020年第12期2027-2031,共5页Central South Pharmacy

基　　金：湖南省卫健委基金课题(No.B20180252);湖南省自然科学基金(No.2018JJ6032)。

摘　　要：厄洛替尼与吉非替尼作为第一代小分子酪氨酸激酶抑制剂(TKI)类靶向药物,目前在临床上广泛地应用于晚期非小细胞肺癌(NSCLC)的治疗。与传统的标准铂二联化疗方案相比,厄洛替尼与吉非替尼能显著提高NSCLC患者的无进展生存期(PFS),且毒副反应较低。但在临床应用中发现,厄洛替尼与吉非替尼在患者内个体差异较大,在标准给药剂量下,有一部分患者出现治疗无效或效果较差的现象,另一部分患者则出现严重的毒副反应。大量的研究表明,代谢酶及转运体基因多态性是引起TKI类小分子靶向药物药动学差异的重要原因。因此,开展基于代谢酶及转运体基因多态性的个体化给药对厄洛替尼与吉非替尼具有重要的意义。本文综述了代谢酶(CYP3A4、CYP3A5、CYP1A1、CYP1A2、CYP2D6)及转运体(ABCB1、ABCG2)基因多态性对NSCLC患者体内厄洛替尼与吉非替尼的治疗效果及毒副反应的影响,为NSCLC患者个体化治疗奠定基础。As the first generation small-molecule tyrosine kinase inhibitor,erlotinib and gefitinib had been widely used for advanced non-small cell lung cancer (NSCLC).In comparison with the traditional standard platinum doublet chemotherapy,erlotinib and gefitinib have dramatically improved the progression-free survival of NSCLC,with fewer adverse events.Despite their striking efficacy,the real-world clinical evidence demonstrated considerable individual variability in both therapeutic efficacy and toxicity.Suboptimal response and response failure to the treatment were also observed in the clinical treatment.In addition,most patients experienced drug-related adverse events with fixed dose erlotinib/gefitinib during their treatment course.More and more evidence recognized that genetic polymorphism of drug-metabolizing enzymes and transporters may significantly influence the inter-individual variations.It is important to conduct genetic polymorphism analysis for NSCLC patients who receive erlotinib or gefitinib at a fixed dose.This review summarized the effect of drug-metabolizing enzymes and transporters on the treatment efficiency and adverse events of erlotinib and gefitinib in NSCLC,which paving the way for individualized treatment of NSCLC.

关 键 词：厄洛替尼 吉非替尼 代谢酶 转运体 基因多态性 

分 类 号：R96[医药卫生—药理学]