非小细胞肺癌治疗中吉非替尼继发耐药的机制研究进展  

Advances in research of acquired drug-resistance of gefitinib in non-small cell lung cancer

作　　者：吉泽[1] 范理宏[1] 

机构地区：[1]上海市第六人民医院肺内科,上海200233

出　　处：《肿瘤》2011年第5期460-464,共5页Tumor

基　　金：上海市卫生局科研课题计划项目(编号:054014)

摘　　要：吉非替尼(gefitinib)是表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosinekinase inhibitors,EGFR-TKIs)类靶向药物,目前主要用于治疗已接受过铂类为基础化疗的非小细胞肺癌进展期患者。然而,靶向药物同样存在着继发耐药的问题。关于继发耐药的相关研究中,目前普遍认同是表皮生长因子受体(epidermal growth factor receptor,EGFR)基因的二次突变学说;但亦有研究显示,吉非替尼的耐药与药物的转运、EGFR/Met基因的扩增以及信号通路的改变有关,非单一机制能完全解释其耐药性。因此,本文将对目前关于吉非替尼继发耐药的机制以及克服耐药的策略的研究进展作一综述。Gefitinib,a tyrosine kinase inhibitor（TKI） of epidermal growth factor receptor（EGFR）,is presently used to treat the patients previously undergoing platinum-based chemotherapy for advanced non-small cell lung cancer（NSCLC）.However,acquired resistance to EGFR-targeting drugs has become a significant problem.Currently,the theory of secondary mutation of EGFR gene was widely accepted in this area.Meanwhile,some studies have shown that gefitinib resistance was related to drug transport,EGFR/Met gene amplification and the changes in signaling pathway,which indicates that this theory can not completely explain the mechanism of acquired drug-resistance.This review will summarize the mechanism of gefitinib resistance,and address the new strategies to overcome this acquired drug-resistance.

关 键 词：癌 非小细胞肺 抗药性 肿瘤 蛋白激酶抑制剂 分子药理作用机制 吉非替尼 

分 类 号：R734.2[医药卫生—肿瘤] R730.53[医药卫生—临床医学]