Université de Lyon-Centre Léon Berard, 28 rue Laennec, 69373 Lyon cedex 08, France.
Invest New Drugs. 2012 Aug;30(4):1791-801. doi: 10.1007/s10637-011-9677-6. Epub 2011 May 15.
Several angiogenic mechanisms are involved in the pathology of renal cell carcinoma (RCC). Increasing knowledge of angiogenesis and the associated signalling pathways has led to the development of targeted antiangiogenic agents for the treatment of metastatic RCC and the introduction of these agents has significantly improved outcomes for these patients. This article provides an overview of the angiogenic mechanisms implicated in RCC, focusing on the main vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and mammalian target of rapamycin (mTOR) signalling pathways. Targeted antiangiogenic agents for the treatment of mRCC include receptor tyrosine kinase inhibitors (such as sunitinib, sorafenib, pazopanib, axitinib, cediranib and tivozanib), monoclonal antibodies (such as bevacizumab) and mTOR inhibitors (such as temsirolimus and everolimus). In this article, we consider the modes of action of these targeted agents and their differing target receptor profiles and we also evaluate how these correlate with their clinical efficacy and tolerability profiles.
几种血管生成机制参与了肾细胞癌（RCC）的病理学过程。对血管生成和相关信号通路的认识不断加深，促使人们开发出针对转移性 RCC 的靶向抗血管生成药物，并显著改善了这些患者的预后。本文概述了 RCC 中涉及的血管生成机制，重点介绍了主要的血管内皮生长因子（VEGF）、血小板衍生生长因子（PDGF）和哺乳动物雷帕霉素靶蛋白（mTOR）信号通路。用于治疗 mRCC 的靶向抗血管生成药物包括受体酪氨酸激酶抑制剂（如舒尼替尼、索拉非尼、帕唑帕尼、阿昔替尼、西地尼布和替沃扎尼）、单克隆抗体（如贝伐珠单抗）和 mTOR 抑制剂（如替西罗莫司和依维莫司）。在本文中，我们考虑了这些靶向药物的作用模式及其不同的靶受体谱，并评估了这些与它们的临床疗效和耐受性谱的相关性。
