晚期非小细胞肺癌MET扩增介导获得性耐药的研究进展

Research Progress of Acquired Resistance Mediated by MET Amplification in Advanced Non-small Cell Lung Cancer

间质-上皮细胞转化因子(mesenchymal-epithelial transition factor,MET)扩增是表皮生长因子受体(epidermal growth factor receptor,EGFR)阳性非小细胞肺癌(non-small cell lung cancer,NSCLC)耐药的重要驱动因素,MET-酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)联合EGFR-TKIs的治疗策略可以克服MET介导的获得性耐药。研究表明,MET扩增也是间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)、RET、ROS1等驱动基因阳性NSCLC患者接受TKIs类药物治疗后耐药的驱动因素。本文综述了近年来关于MET扩增作为驱动基因阳性NSCLC靶向治疗耐药驱动因素的研究进展,并总结了克服这种耐药机制的治疗策略。

Mesenchymal-epithelial transition factor(MET)amplification is an important driver of resistance in epidermal growth factor receptor(EGFR)-mutant non-small cell lung cancer(NSCLC),and the combination of MET protooncogene(MET)and EGFR-tyrosine kinase inhibitors(TKIs)has shown promise in overcoming this molecularly defined acquired resistance.Emerging data also demonstrate MET amplification as a resistance driver to TKIs-treated anaplastic lymphoma kinase(ALK)-,RET-,and ROS1-fusion NSCLC.Here,we review the literature on recent research progress of MET amplification as a resistance driver to targeted therapy in oncogene-driven NSCLC and summarize the progress of clinical strategies to overcome the resistance mechanism.