Crizotinib在ALK基因阳性非小细胞肺癌中的临床研究进展

摘要

Crizotinib是小分子ATP竞争性抑制剂,对间变性淋巴瘤激酶(ALK)和肝细胞生长因子受体(c-Met/HGFR)以及它们的致癌变异体有选择性抑制作用.在临床研究PROFILE 1001和PROFILE 1005中,ALK重排阳性NSCLC患者对crizotinib有效率达50％～ 60％,大多数不良反应为1～2度.Vysis ALK breakapart FISH probe kit为检测ALK重排的标准方法.ALK重排更易出现在不吸烟或少吸烟的肺腺癌患者中.crizotinib的耐药机制比较复杂.%Crizotinib is a selective ATP-competitive inhibitor of anaplastic lymphoma kinase (ALK), hepatocyte growth factor receptor(c-Met/HGFR) tyrosine kinases and their oncogenic variants. In PROFILE 1001 and PROFILE 1005 clinical trials, the response rate of crizotinib is 50% ~ 60% for non-small cell lung cancer(NSCLC) patients with ALK rearrangement. Most of the adverse events are grade 1 ~2. Vysis ALK breakapart FISH probe kit is a standard diagnostic test to detect ALK-rearrangement. ALK-rearrangement is more often seen in never/light smokers with lung adenocarcinomas. The mechanism of crizotinib resistance is complicated.