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Clin Cancer Res. 2006 Dec 15;12(24):7215-20.

Targeting von Hippel-Lindau pathway in renal cell carcinoma.

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  • 1Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.


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 alpha 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 alpha 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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