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Editor’s note: The development of sporadic clear-cell renal cell carcinoma (RCC) is now known to be driven by inactivation of the von Hippel–Lindau gene. This can occur through mutations in the gene itself or gene silencing as a result of hypermethylation. The result is an abnormal accumulation of hypoxia-inducible factor-1
α, which in turn upregulates factors such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). These factors ultimately promote increased tumor growth and metastasis. For this reason, the VEGF and PDGF receptors have been considered to be important therapeutic targets in RCC, with several agents such as sunitinib and sorafenib demonstrating high levels of activity in recent years. Pazopanib is a novel small-molecule tyrosine kinase inhibitor that targets the VEGF, PDGF, and c-KIT receptors. This drug has previously demonstrated some activity in patients with refractory RCC in the Phase I setting (
Clin Cancer Res 2009;15:4220–7).