抗VEGF/VEGFR靶向肿瘤血管药物的研究进展

研究表明,肿瘤的生长转移和新血管的生成有密切关系,其中血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)及其信号途径在肿瘤血管生成中起关键作用。阻断该途径的任何环节均可有效抑制肿瘤血管的生成,进而抑制肿瘤的生长和转移。近年来,已有多种以VEGF/VEGFR为靶点的抗肿瘤血管生成药物投入临床应用,其中bevacizumab为第一个获批上市的抗肿瘤血管生成药物。继bevacizumab后,一种以基因工程手段获得的人Fc融合蛋白Zaltrap也成功在美国上市,这种杂交分子的药代动力学明显优于单克隆抗体,能更好的遏制肿瘤血管的发生并消退已形成的肿瘤血管。在肿瘤的临床治疗中,Zaltrap比bevacizumab显示出更大的优势。此外,VEGFC/D Trap及小分子酪氨酸激酶抑制剂也能有效抑制肿瘤血管的生成。在此对以VEGF/VEGFR为靶点的抗肿瘤血管生成药物进行综述。

Progress in Anti-tumor Angiogenesis Drugs Targeting VEGF/VEGFR

Tumor growth and metastasis depend on angiogenesis, vascular endothelial growth factor （VEGF）and its signaling pathway play a key role in tumor-associated angiogenesis. Blocking any step in this pathway can effectively inhibit the tumor-associated angiogenesis and thereby inhibit the growth and metastasis of tumor. In recent years, there have been many anti-tumor angiogenesis drugs that target VEGF/VEGFR in clinical application, in which bevacizumab was the first one approved. After bevacizumab, Zaltrap, a human Fc fusion protein which was structured by genetic engineering, was also successful on sale in America. Pharmacokinetics of the fusion protein is significantly better than that of the monoclonal antibodies. In the therapeutics to tumor, Zaltrap shows greater advantage than bevacizumab. In addition, VEGFC/D Trap and tyrosine kinase inhibitors can also effectively inhibit tumor-associated angiogenesis. This review aimed to summarize the anti-tumor angiogenesis drugs which target VEGF/VEGFR.