Department of Pharmaceutical Chemistry, ISF College of Pharmacy, India.
Mini Rev Med Chem. 2013 Apr;13(4):530-40. doi: 10.2174/1389557511313040006.
Angiogenesis is the process of formation of new blood vessels due to over expression of VEGF (vascular endothelial growth factor) which plays a critical role in the growth and development of all solid tumor types. With the advancement in understanding of tumor angiogenesis and VEGF, there have been a number of agents developed to target VEGF for the treatment of cancer. These targeted agents can affect downstream VEGF signal transduction by unique mechanisms at different cellular and extracellular levels. FDA has recently approved Aflibercept or VEGF-Trap in August 2012 for the treatment of colorectal cancer. It is a recombinant, decoy receptor fusion protein, rationally designed to block angiogenesis by targeting VEGF-A, VEGF-B and placental growth factor. VEGF-Trap exerts its antiangiogenic effects through regression of tumor vasculature, remodelling or normalization of surviving vasculature and inhibition of new tumor vessel growth. In this review, pre-clinical and clinical data have been summarized for aflibercept alone and in combination with chemotherapy to explore its efficacy and benefits in ovarian cancer, breast cancer, non-small cell lung cancer, pancreatic cancer, glioblastoma, adenocarcinoma and renal cell cancer xenograft models.
血管生成是新血管形成的过程，这是由于 VEGF（血管内皮生长因子）的过度表达所致，VEGF 在所有实体肿瘤类型的生长和发育中起着关键作用。随着对肿瘤血管生成和 VEGF 的理解的提高，已经开发出许多针对 VEGF 的药物来治疗癌症。这些靶向药物可以通过独特的机制在不同的细胞和细胞外水平上影响下游的 VEGF 信号转导。FDA 最近于 2012 年 8 月批准了 Aflibercept（阿柏西普）或 VEGF-Trap（贝伐珠单抗）用于治疗结直肠癌。它是一种重组的、诱饵受体融合蛋白，通过靶向 VEGF-A、VEGF-B 和胎盘生长因子来合理设计以阻断血管生成。VEGF-Trap 通过肿瘤血管的退化、存活血管的重塑或正常化以及新肿瘤血管生长的抑制来发挥其抗血管生成作用。在这篇综述中，总结了阿柏西普单独使用和与化疗联合使用的临床前和临床数据，以探索其在卵巢癌、乳腺癌、非小细胞肺癌、胰腺癌、胶质母细胞瘤、腺癌和肾细胞癌异种移植模型中的疗效和益处。
