Angiogenesis and angiogenic inhibitors in renal cell carcinoma.

In most patients with renal cell carcinoma (RCC) of clear cell subtype, there is inactivation of the von Hippel-Lindau (VHL) tumor-suppressor gene, which leads to a proangiogenic state with overexpression of vascular endothelial growth factor (VEGF). This molecular level knowledge has led to the development of multiple antiangiogenic therapies directed against the VEGF protein or the VEGF receptor. These therapies have significant clinical activity in metastatic RCC. Therefore, a therapeutic strategy based on targeting VEGF in RCC has a sound molecular basis and therapy with VEGF-targeting agents has significant clinical activity. To further improve efficacy, future research should focus on better identification of patients who will most benefit from such therapy. We reviewed the published literature regarding angiogenesis, the VHL gene, VEGF biology, and antiangiogenic therapies in metastatic RCC. This article reviews the role of angiogenesis in RCC and summarizes data regarding antiangiogenic therapy in metastatic RCC.