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lüll Targeting von Hippel-Lindau pathway in renal cell carcinoma Patel PH; Chadalavada RS; Chaganti RS; Motzer RJClin Cancer Res 2006[Dec]; 12 (24): 7215-20Inheritance 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.|Benzenesulfonates/therapeutic use[MESH]|Biomedical Research/trends[MESH]|Carcinoma, Renal Cell/*drug therapy[MESH]|Enzyme Inhibitors/chemistry/*therapeutic use[MESH]|Everolimus[MESH]|Humans[MESH]|Indoles/therapeutic use[MESH]|Kidney Neoplasms/*drug therapy[MESH]|Models, Biological[MESH]|Niacinamide/analogs & derivatives[MESH]|Phenylurea Compounds[MESH]|Pyridines/therapeutic use[MESH]|Pyrroles/therapeutic use[MESH]|Signal Transduction[MESH]|Sirolimus/analogs & derivatives/therapeutic use[MESH]|Sorafenib[MESH]|Sunitinib[MESH]|Von Hippel-Lindau Tumor Suppressor Protein/*antagonists & inhibitors/physiology[MESH] |