Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis. VEGF expression in metastatic renal cell carcinoma (mRCC) is mostly regulated by hypoxia, predominantly via the hypoxia-induced factor (HIF)/Von Hippel-Lindau (VHL) pathway. Advances in our knowledge of VEGF role in tumor angiogenesis, growth, and progression have permitted development of new approaches for the treatment of mRCC, including several agents targeting VEGF and VEGF receptors: tyrosine kinase pathway, serine/threonine kinases, α5β1-integrin, deacetylase, CD70, mammalian target of rapamycin (mTOR), AKT, and phosphatidylinositol 3′-kinase (PI3K). Starting from sorafenib and sunitinib, several targeted therapies have been approved for mRCC treatment, with a long list of agents in course of evaluation, such as tivozanib, cediranib, and VEGF-Trap. Here we illustrate the main steps of tumor angiogenesis process, defining the pertinent therapeutic targets and the efficacy and toxicity profiles of these new promising agents.
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机译：血管内皮生长因子（VEGF）在肿瘤血管生成中起关键作用。转移性肾细胞癌（mRCC）中的VEGF表达主要受低氧调节，主要通过低氧诱导因子（HIF）/ Von Hippel-Lindau（VHL）途径进行。我们对VEGF在肿瘤血管生成，生长和进展中的作用的了解不断发展，因此允许开发出新的mRCC治疗方法，包括针对VEGF和VEGF受体的几种药物：酪氨酸激酶途径，丝氨酸/苏氨酸激酶，α5β1-整联蛋白，脱乙酰酶，CD70，雷帕霉素（mTOR），AKT和磷脂酰肌醇3'-激酶（PI3K）的哺乳动物靶标。从索拉非尼和舒尼替尼开始，已经批准了几种靶向疗法用于mRCC治疗，并且正在评估中的药物包括tivozanib，西地那尼和VEGF-Trap。在这里，我们说明了肿瘤血管生成过程的主要步骤，定义了相关的治疗靶标以及这些新的有前景药物的疗效和毒性谱。
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