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Molecular Pathways |
Authors' Affiliations: 1 Department of Medicine and 2 Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York
Requests for reprints: Robert J. Motzer, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. Phone: 646-422-4312; Fax: 212-988-0806; E-mail: motzerr{at}mskcc.org.
Abstract
Inheritance of a defective copy of the von Hippel-Lindau (VHL) gene leads to the most common cause of inherited renal cell carcinoma (RCC). In addition, most patients with sporadic RCC have aberrant VHL. In the absence of VHL, hypoxia-inducible factor 
accumulates, leading to production of several growth factors, including vascular endothelial growth factor and platelet-derived growth factor. We review here the biology of RCC and how a combination of proximal and distal block of VHL/hypoxia-inducible factor pathway by novel targeted agents, including sunitinib, sorafenib, bevacizumab, everolimus, and temsirolimus, has led to significant improvements in progression-free survival.
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