靶向肿瘤血管生成的晚期非小细胞肺癌治疗策略进展

Advances in the targeting tumor angiogenesis as a therapeutic strategy in non-small cell lung cancer

肿瘤血管生成通路是包括非小细胞肺癌(non-small cell lung cance,NSCLC)在内的多种肿瘤治疗策略中一个重要的治疗靶点。血管生成是原发性肿瘤发生、增殖及转移的关键进程和环节。目前发现的诱导肿瘤新生血管生成最重要的细胞因子是血管内皮生长因子(vascular endothelial growth factor,VEGF)家族蛋白,而VEGF和相应受体是血管生成相关分子机制中最核心的信号通路。针对NSCLC的靶向抗血管治疗主要作用途径为:直接阻止VEGF与血管内皮生长因子受体(vascular endothelial growth factor receptor,VEGFR)结合的单克隆抗体、抑制VEGFR介导的下游信号通路的小分子酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)。目前,多种抗血管生成药物获得了NSCLC治疗的多个适应证,并在单独或联合化疗、靶向治疗、免疫治疗的多项NSCLC的临床研究中得到了应用并进行疗效评估。

In many cancers, including non-small cell lung cancer（NSCLC）, tumor angiogenesis pathways have been identified as important therapeutic targets. Angiogenesis is essential in the process of primary tumor growth, proliferation and metastasis. One of the best characterized and vital groups of protein factors including the members of the vascular endothelial growth factor（VEGF） family, VEGF and its receptors are the most important signaling pathways in angiogenesis related molecular mechanisms. Targeting tumor angiogenesis has been approached through monoclonal antibodies that block VEGF-vascular endothelial growth factor receptor（VEGFR） binding or small molecule tyrosine kinase inhibitors（TKIs） that inhibit the downstream VEGFR mediated signaling. At present, various anti angiogenic drugs have obtained multiple indications for NSCLC treatment, and it has been applied and evaluated in many clinical studies, including single use or combined chemotherapy, targeted therapy and immunotherapy.