非小细胞肺癌T790M基因突变研究进展

Advanced Research on T790M Mutation in Non-small Cell Lung Cancer

携带表皮生长因子受体(epidermal growth factor receptor,EGFR)基因活性突变的非小细胞肺癌(non-small cell lung cancer,NSCLC)晚期患者使用EGFR-受体酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)治疗后具有较好的临床获益,但大部分患者在使用该药治疗10个月后出现耐药现象。研究发现EGFR基因20号外显子T790M基因突变是导致EGFR-TKI耐药的最主要因素,但其作用机制至今未明。目前的研究结果显示T790M基因突变是一个独立的、好的预后因素,但其能否作为EGFR-TKI的疗效预测因子仍存在争议。近年来,针对NSCLC肿瘤中T790M基因突变的检测技术不断更新,针对T790M耐药的新的治疗策略也不断涌现。本文就NSCLC中T790M基因突变的耐药机制、临床意义、检测方法及应对策略等方面的最新研究进展进行综述。

Patients with advanced non-small cell lung cancer （NSCLC） carrying epidermal growth factor receptor （EGFR） activating mutations benefit from EGFR-tyrosine kinase inhibitor （TKI） treatment, however, most of TKI-treated patients eventually suffer drug resistant after 10-month treatments. Previous studies demonstrated that T790M mutation in exon 20 of EGFR gene would be the essential factor leading to EGFR-TKI resistance, leaving the mechanisms of which elucidative. Current research identified that T790M is an independent, favorable prognostic factor for predicting survival, but whether it is also a predictive biomarker for EGFR-TKI efficacy is still controversial. Up to date, techniques to detect T790M mutation in lung cancer have been greatly improved and the new therapeutic strategies emerged as well. In this review, we summarized the newly updated data about T790M mutation in terms of its mechanisms involved in EGFR-TKI resistant, clinical value, advanced detection assays and ongoing strategies against the mutation subtype.