伴T790M突变的晚期非小细胞肺癌患者的治疗及耐药机制研究进展

Research Process on Treatment and Mechanism of Drug-resistance in Non-small Cell Lung Cancer Patient with T790M Mutation

表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitors,EGFR-TKIs)已被列为晚期非小细胞肺癌患者的一线用药。第一代和第二代TKIs在为患者带来临床益处的同时,也不可避免的导致了耐药,其中最为常见的机制是T790M突变,见于50%~60%对一二代TKIs耐药的患者。奥希替尼,作为唯一一个获得认证的针对EGFR-T790M突变的第三代TKIs,可以有效克服该种突变导致的耐药,临床上已有大量数据支持该结论。然而,耐药总是难以避免,其耐药机制大致分为EGFR依赖型和EGFR非依赖型两类。本文就EGFR-T790M突变的治疗以及奥希替尼耐药机制简要进行综述,以期对未来临床治疗和基础研究提供思路。

Epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs) have become the standard therapy as first-line treatment of advanced non-small cell lung cancer.The first or second generation TKIs which have benefited patients a lot will also lead to resistance to these inhibitors,inevitably,and the most common mechanism is T790M mutation,which can been identified in 50%-60% patients who are resistance to the first or second generation of TKIs.Osimertinib,as the only certified third-generation TKIs targeting EGFR-T790M mutation,can effectively overcome the resistance caused by this mutation,a large number of clinical data have supported this conclusion.However,the acquired resistance to drug is inevitable,and the mechanism of drug-resistance can be clarified two groups which are called EGFR-dependent pathway and EGFR-independent pathway respectively.This paper is trying to review the therapy for patients with EGFR sensitive mutation and T790M mutation and the potential mechanism of drug-resistance to Osimertinib and wishes to provide some inspiration to the clinical treatment and basic research in the future.