Given that VHL inactivation leads to inappropriate angiogenesis in both sporadic and germline VHL-disease associated lesions, tyrosine kinase inhibitors against the VEGF pathway, such as sunitinib and pazopanib, are approved treatment approaches for metastatic ccRCC and are just some of the inhibitors being actively investigated for treatment of VHL disease. This evidence concerns the gene VHL and nonpapillary renal cell carcinoma.