VEGFA and nonpapillary renal cell carcinoma: In most ccRCC patients who lack VHL, HIF-1α, and HIF-2α improve oxygen delivery through hypervascularization, thus promoting tumor formation.[18,19] Drugs that target angiogenesis or vascular endothelial growth factor (VEGF) monoclonal antibodies are, therefore, the primary option for targeted therapy in RCC.