表皮生长因子受体和血管内皮细胞生长因子受体之外肺癌靶向治疗新进展

Targeted therapies for lung cancer beyond anti-epidermal growth factor receptors and anti-vascular endothelial cell growth factor receptors:exploring a new frontier

目前肺癌的生物靶向治疗已进入临床治疗阶段,以吉非替尼、厄洛替尼和西妥昔单抗为代表的抗表皮生长因子受体(epidermal growth factor receptor,EGFR)通路的药物和以贝伐单抗为代表的抗血管内皮细胞生长因子受体(vascular endothelialcell growth factor receptor,VEGFR)通路的药物已成功地应用于肺癌临床治疗。然而,肺癌分子生物学机制十分复杂,以EGFR和VEGFR信号通路为靶点的治疗存在局限和不足。近年来,肺癌新的分子生物靶点逐渐受到关注,例如棘皮动物微管相关蛋白4/间变淋巴瘤激酶(echinoderm microtubule-associated protein-like4/anaplastic lymphoma kinase,EML4-ALK)融合基因、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)、胰岛素样生长因子Ⅰ型受体(insulin-like growth factor typeⅠreceptor,IGF-1R)和间质上皮转变因子(mesenchymal-epithelial transition factor,c-MET)等。本文对上述分子生物学标志物在肺癌治疗中的作用及其相关临床研究进展进行综述。

Nowadays, targeted therapies for lung cancer have entered into the clinical phase. Anti-epidermal growth factor receptor （EGFR） drugs, such as gefitinib and elotinib, and anti-vascular endothelial cell growth factor receptor （VEGFR） agent bevaci- zumab have been successfully applied in the clinical treatment of lung cancer. However, the mechanism for tumorigenesis of lung cancer is complicated. Anti-EGFR and anti-VEGFR therapy have some limitations and weakness. In recent years more and more attention has been focused on some new molecular targets in lung cancer, such as echinoderm microtubule-associated protein-like-4/anaplastic lymphoma kinase （EML4-ALK） fusion gene, mammalian target of rapamycin （mTOR）, insulin-like growth factor type I receptor （IGF- 1 R）, and mesenchymal epithelial transition factor （ c-MET）, and so on. In the present paper we review the roles of these new biomarkers in lung cancer therapy and the progress in clinical research.