Clinical implications of hypoxia inducible factor in renal cell carcinoma

Management of renal cell carcinoma (RCC) has made considerable strides in the past decade, due in large part to identification of the von Hippel Lindau (VHL) tumor suppressor as a negative regulator of hypoxia inducible factor alpha (HIF-alpha) protein expression. Stabilization of HIF-alpha appears to be critical for renal tumorigenesis, and is observed even in VHL-independent RCC. Thus, an understanding of the pathways that regulate expression and activation of the different HIF-alpha isoforms is key to delineating the mechanism of renal transformation and for the development of novel therapeutics. A number of agents targeting HIF-alpha or its transcriptionally-regulated genes have shown promise in treatment of RCC. However, more effective treatment strategies are still needed. This report provides a directed review of recent discoveries defining the role of HIF in renal tumorigenesis and their relevance to the clinical advances in targeted therapy for advanced RCC. (C) 2009 Elsevier Inc. All rights reserved.