中国癌症杂志 ›› 2013, Vol. 23 ›› Issue (4): 308-314.doi: 10.3969/j.issn.1007-3969.2013.04.012

• 综述 • 上一篇    下一篇

EGFR TKIs在非小细胞肺癌中的耐药机制及治疗进展

王珊珊 综述常建华 审校   

  1. 复旦大学附属肿瘤医院化疗科,复旦大学上海医学院肿瘤学系,上海200032
  • 出版日期:2013-04-25 发布日期:2014-11-19
  • 通信作者: 常建华 E-mail:changjianhua@163.com

Mechanisms of resistance to EGFR TKIs and therapeutic perspectives in non-small cell lung cancer

WANG Shan-shan, CHANG Jian-hua   

  1. Department of Chemotherapy, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
  • Published:2013-04-25 Online:2014-11-19
  • Contact: CHANG Jian-hua E-mail: changjianhua@163.com

摘要:

吉非替尼和厄洛替尼是表皮生长因子受体(epidermal growth factor receptorEGFR)酪氨酸激酶抑制剂(tyrosine kinase inhibitorsTKIs),广泛用于非小细胞肺癌的治疗。但随着应用的深入,耐药问题开始凸显。过去几年,针对继发性耐药和原发性耐药的深入研究,发现EGFR二次突变,MET基因扩增,K-ras基因突变等是EGFR TKIs耐药的主要原因。本文就EGFR-TKIs原发耐药与继发耐药的机制,以及克服此类耐药的新型药物及其临床试验数据作一综述。

关键词: 耐药, 突变, 信号通路, 治疗

Abstract:

Gefitinib and erlotinib, which are epidermal growth factor receptor (EGFR) specific tyrosine kinase inhibitors (TKIs), are widely used as molecularly targeted drugs for non-small-cell lung cancer (NSCLC). However, many patients ultimately develop resistance to these drugs. Mechanisms of acquired and primary resistance have been reported in the past few years, such as secondary mutation of the EGFR gene, amplification of the MET gene and mutations of the K-ras gene. Novel pharmaceutical agents are currently being developed to overcome resistance. This review focuses on these mechanisms of resistance to EGFR-TKIs and discusses how can be overcome.

Key words: Resistance, Mutation, Signaling pathway, Therapy