克唑替尼治疗肺癌的疗效及其耐药后的治疗

以棘皮动物微管相关蛋白4-间变性淋巴瘤激酶（EML4-ALK）融合基因突变为靶点的酪氨酸激酶抑制剂（TKI）克唑替尼能够显著延长晚期 ALK 阳性非小细胞肺癌（NSCLC）患者的无进展生存期（PFS），一线、二线单药治疗的中位 PFS 分别为10．9个月和7．7个月。尽管克唑替尼的初始疗效良好，但大部分患者于治疗1年内出现耐药并显示疾病复发，其原因是 ALK 融合基因扩增和二次突变。临床试验证实二代 ALK 抑制剂、联合热休克蛋白等能有效克服克唑替尼耐药。

Therapeutic effects of crizotinib in lung cancer and the treatment after drug resistance

Crizotinib is a tyrosine kinase inhibitor (TKI),which is a target for echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK).It can prolong the progression free survival (PFS)of ALK positive patients with advanced non-small cell lung cancer (NSCLC).The median PFS in the first-line and second-line mPFS is 10.9 months and 7.7 months.However,despite an initial benefit,patients inevitably experience tumor progression,due to the ALK fusion gene amplification and secondary mutations of ALK kinase domain.Clinical trials show the promising efficacy like next generation ALK inhibitors and heat shock protein 90 (HSP90)can overcome acquired resistance.