Renal cell carcinoma: rationale and development of therapeutic inhibitors of angiogenesis
Renal cell carcinoma: rationale and development of therapeutic inhibitors of angiogenesis
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DOI：
10.1016/j.hoc.2004.06.003
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发表时间：
2004-10-01
影响因子：
2.4
通讯作者：
Gordon, MS
中科院分区：
文献类型：
--
作者：
Ebbinghaus, SW;Gordon, MS
抑制肿瘤血管生成是治疗癌症的一种有前途的治疗方法;将这一概念转化为临床实践需要了解负责肿瘤血管发展的分子事件。肾细胞癌的特征在于von Hippel Lindau肿瘤抑制基因的频繁丢失，这导致调节缺氧诱导因子1水平的关键机制之一的丢失，并导致肿瘤细胞过度产生血管内皮生长因子（VEGF）。抑制这些重要途径功能的治疗策略在肾癌临床前模型中以及最近在临床环境中有效预防肿瘤血管生成。用设计用于预防血管生成的药物治疗肾细胞癌的策略包括阻断VEGF信号通路、模拟内源性血管生成抑制剂、预防基底膜破坏以及通过具有复杂、新颖或未确定机制的多种药物直接抑制内皮细胞。贝伐单抗是第一种上市用于治疗癌症的抗VEGF药物，最近的临床研究证明了这些策略可以为晚期肾细胞癌患者带来实实在在的益处，并可能广泛适用于癌症治疗。
Inhibition of tumor angiogenesis is a promising therapeutic approach to treat cancer; translation of this concept into clinical practice requires an understanding of the molecular events that are responsible for the development of tumor vasculature. Renal cell carcinoma is characterized by the frequent loss of the von Hippel Lindau tumor suppressor gene, which results in the loss of one of the critical mechanisms for regulating the level of hypoxia inducible factor 1 and leads to the overproduction of vascular endothelial growth factor (VEGF) by the tumor cell. Therapeutic strategies to inhibit the function of these important pathways have been effective in preventing tumor angiogenesis in preclinical models of kidney cancer, and more recently, in the clinical setting. Strategies to treat renal cell carcinoma with agents that are designed to prevent angiogenesis have included interruption of the VEGF signaling pathway, mimics of endogenous angiogenesis inhibitors, prevention of destruction of the basement membrane, and direct inhibition of endothelial cells by a variety of agents with complex, novel, or undetermined mechanisms. Recent clinical studies of bevacizumab, the first anti-VEGF agent to be marketed for the treatment of cancer, have provided proof for the concept that these strategies can lead to tangible benefits for patients who have advanced renal cell carcinoma and likely will be applicable broadly to the treatment of cancer.