二代表皮生长因子受体酪氨酸激酶抑制剂在肺癌中的应用

Development of second-generation EGFR TKIs in lung cancer treatment

表皮生长因子受体(epidermal growth factor receptor,EGFR)的发现和EGFR酪氨酸激酶抑制剂(EGFR tyrosine kinase inhibitors,EGFR TKIs)在敏感突变阳性肺癌患者中的应用,是肺癌治疗史上里程碑式的进展。与标准化疗相比,EGFR TKIs显著地延长了这类患者的无进展生存期,但所有患者都不可避免地会对EGFR TKIs产生耐药。为了克服耐药问题,应运而生的新型EGFR TKIs在作用靶点、结合方式以及临床疗效上均有一定程度的创新和突破,因而被称为"二代EGFR TKIs"。本文就二代EGFR TKIs在肺癌中的研究进展加以综述。

The discovery of activating mutations in EGFR（epidermal growth factor receptor） and the approval of EGFR tyrosine kinase inhibitors（TKIs） are the mailstone in the treatment of non-small cell lung cancer（NSCLC）.First-generation EGFR TKIs have（gefitinib and erlotinib） greatly improved the progression free survival compared with standard chemotherapy in EGFR-positive NSCLC.Yet almost all patients eventually progress due to the emergence of resistance.Second-generation EGFR TKIs are the most potential agents to overcome or delay the resistance to first-generation EGFR TKIs,which have improvements in target,binding form and efficacy.Here,we reviewed the development of second-generation EGFR TKIs.