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Original Paper Genitourinary Cancer

VEGF-Targeted Therapy in Metastatic Renal Cell Carcinoma

The University of California San Francisco Comprehensive Cancer Center, San Francisco, California, USA

Correspondence: Brian I. Rini, M.D., 1600 Divisadero, Room A717, San Francisco, California 94115, USA. Telephone: 415-353-7095; Fax: 415-353-7779; e-mail: brini{at}medicine.ucsf.edu

Purpose. To review the biology of renal cell carcinoma (RCC) and the clinical results of vascular endothelial growth factor (VEGF) blockade in metastatic RCC.

Methods. A review of relevant published literature regarding VEGF, von Hippel-Lindau (VHL) gene inactivation, and VEGF overexpression in RCC was performed. Further, a review of the mechanism, toxicity, and clinical development of VEGF-targeted therapy in metastatic RCC was undertaken.

Results. VHL tumor suppressor gene inactivation is observed in the majority of clear cell RCC cases, leading to VEGF overexpression. Therapy with agents directed against the VEGF protein or the VEGF receptor have demonstrated initial clinical activity in metastatic RCC.

Conclusions. Therapeutic targeting of VEGF in RCC has strong biologic rationale. Substantial clinical activity has been reported in initial clinical trials with VEGF-targeting agents. Further investigation is needed to optimally use these agents for maximal clinical benefit.

Key Words. RCC • VEGF • VHL • Bevacizumab • SU11248 • BAY 43-9006

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