VEGF-targeted therapy in metastatic renal cell carcinoma.
OBJECTIVE
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.
Rini
Brian I
BI
1600 Divisadero, Room A717, San Francisco, California 94115, USA. brini@medicine.ucsf.edu
D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D009362:Neoplasm Metastasis; D025521:Tumor Suppressor Proteins / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology*; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human