非小细胞肺癌中EGFR突变与EGFR-TKI临床敏感性及耐药性的研究进展

Development on the relation between EGFR mutation and EGFR-TKI sensitivity and resistance in NSCLC

目的阐述非小细胞肺癌(NSCLC)中表皮生长因子受体(EGFR)突变与表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)临床敏感性及耐药性之间的关系。方法分析总结已经发表的国内外相关文献,对非小细胞肺癌治疗中EGFR-TKI的敏感性和耐药性进行介绍。结果在NSCLC患者中用EGFR-TKI治疗有效性和EGFR活化性突变有着紧密的联系,二者都在亚洲人种,女性,不吸烟,腺癌患者中发生率较高;患者对EGFR-TKI耐药不仅与EGFR二次突变有关,还与KRAS突变,HER2过表达,蛋白酪氨酸磷酸酶基因(PTEN)缺失,胰岛素样生长因子受体1(IGFR-1)过表达等有联系。结论EGFR突变可作为临床衡量EGFR-TKI敏感性指标;耐药机制复杂多变,目前还没有完全研究清楚。

Objective To introduce the relation between EGFR（epidermal growth factor receptor） mutation and EGFR-TKI（EGFR tyrosine kinase inhibitor） sensitivity and resistance in NSCLC（non-small cell lung cancer）. Methods Recent literature on EGFR mutations were reviewed and the sensitivity and resistance of non-small cell lung cancer treatment were introduced. Results There was strong relation between EGFR- TKI response and EGFR mutation, both of them had higher efficacy in Asian, females, nonsmokers, adeno- earcinmmas. And the patients with EGFR mutation had stronger response. The relation of resistance is not only with EGFR mutation, but also with KARS mutation, HER2 overexpression, the deletion of PTEN （phosphatase and tensin homolog deleted on chromosome 10）, and IGFR-1 （insulin-like growth factor receptor 1） overexpression. Conclusions It is possible to selecte patients for individualizing EGFR-TKI treatment of lung cancer according to EGFR mutational status and other biomarkers. The mechanism of resistance is complicated and changeable and the present study has not yet completely clear.