Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Moores Cancer Center, University of California San Diego, San Diego, CA 92093, USA.
Int J Mol Sci. 2018 Apr 18;19(4):1232. doi: 10.3390/ijms19041232.
Anti-angiogenic therapy is one of the promising strategies for many types of solid cancers. Bevacizumab (Avastin), a recombinant humanized monoclonal antibody of vascular endothelial growth factor (VEGF) A, was approved for the first time as an anti-angiogenic drug for the treatment of metastatic colorectal cancer (CRC) by the Food and Drug Administration (FDA) in 2004. In addition, the other VEGF pathway inhibitors including small molecule tyrosine kinase inhibitors (sunitinib, sorafenib, and pazopanib), a soluble VEGF decoy receptor (aflibercept), and a humanized monoclonal antibody of VEGF receptor 2 (VEGFR2) (ramucirumab) have been approved for cancer therapy. Although many types of VEGF pathway inhibitors can improve survival in most cancer patients, some patients have little or no beneficial effect from them. The primary or acquired resistance towards many oncological drugs, including anti-VEGF inhibitors, is a common problem in cancer treatment. This review summarizes the proposed alternative mechanisms of angiogenesis other than the VEGF pathway. These mechanisms are involved in the development of resistance to anti-VEGF therapies in cancer patients.
抗血管生成治疗是许多实体瘤的一种有前途的策略。贝伐珠单抗（阿瓦斯汀）是一种血管内皮生长因子（VEGF）A 的重组人源化单克隆抗体，于 2004 年首次被美国食品和药物管理局（FDA）批准作为转移性结直肠癌（CRC）的抗血管生成药物。此外，其他 VEGF 通路抑制剂，包括小分子酪氨酸激酶抑制剂（舒尼替尼、索拉非尼和帕唑帕尼）、可溶性 VEGF 诱饵受体（阿柏西普）和 VEGF 受体 2（VEGFR2）的人源化单克隆抗体（雷莫芦单抗），已被批准用于癌症治疗。尽管许多类型的 VEGF 通路抑制剂可提高大多数癌症患者的生存率，但有些患者几乎没有或没有从中受益。对包括抗 VEGF 抑制剂在内的许多肿瘤药物的原发性或获得性耐药是癌症治疗中的一个常见问题。本文综述了除 VEGF 通路以外的其他血管生成的替代机制。这些机制参与了癌症患者对抗 VEGF 治疗产生耐药性的发展。
