In 2005 and 2006, sorafenib and sunitinib became the first FDA-approved TKI therapies targeting the VEGF receptor based on evidence from phase 3 trials.8,9 The majority of TKI therapies for RCC target the VEGF receptor, a downstream component of the VHL/HIFα pathway, which promotes angiogenesis and tumor proliferation. This evidence concerns the gene VHL and neoplasm.