非小细胞肺癌EGFR-TKI耐药机制及治疗策略

Mechanism and Strategies on Drug Resistance of Non-small Cell Lung Cancer to EGFR-TKI

非小细胞肺癌(non-small cell lung cancer,NSCLC)占全部肺癌的80%,而NSCLC患者中有很大一部分在确诊时已经处于晚期。因此,对于晚期NSCLC的治疗也越来越受到人们的重视。既往晚期NSCLC的标准治疗为含铂双药联合化疗,但化疗药物对改善晚期NSCLC患者的生存期方面作用十分有限。随着医学分子生物学技术的发展和肺癌分子发病机制的研究,以表皮生长因子受体(epidermal growth factor receptor,EGFR)为靶点的分子靶向治疗在NSCLC的治疗中独领风骚。其代表药物为吉非替尼和厄洛替尼,这两种EGFR-TKIs已在全世界范围内得到认可并被广泛用于晚期NSCLC的治疗,尤其是对于EGFR敏感突变者。然而,经过一段时间(中位时间为6~12月)的治疗后,大部分患者会对EGFR-TKIs产生耐药,其耐药机制主要包括原发性和获得性耐药。本文综述了近年来NSCLC耐药机制的新进展及耐药后治疗的新策略。

Non-small cell lung cancer（NSCLC） accounts for about 80% of all lung cancer.There is a great many NSCLC patients have been in advanced stage when diagnosed.As a result,people pay more attention to curing advanced NSCLC.The standard treatment to advanced NSCLC is platinum-based combined chemotherapy.Then exploring new therapies is extremely urgent to us.With the development of medical molecular biology techniques and the study of molecular pathogenesis of lung cancer,epidermal growth factor receptor（EGFR） tyrosine kinase inhibitors（TKIs） such as gefitinib and erlotinib are becoming promising therapies for parts of patients with NSCLC.The compounds which target the EGFR play an important role in the treatment of the NSCLC.However,after a period of treatment（median time is 6 to 12 months）,most patients will develop drug resistance to EGFR-TKIs.Intense research in these NSCLCs has identified two major mechanisms of resistance to TKIs：Primary and acquired resistances.The aim of this article was to summarize the development of the resistance mechanisms and new overcoming strategies on better treatment of drug resistant cancer cells in EGFR-mutant NSCLC.