However, identification of the Von Hippel-Lindau (VHL) tumor-suppressor gene, and that its inactivation in ccRCC led to increased expression of hypoxia-inducible factor alpha (HIF-α) and angiogenesis-related proteins such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor B chain (PDGF-B), led to the development of targeted therapies that specifically inhibit VEGF signaling pathways. This evidence concerns the gene PDGFB and nonpapillary renal cell carcinoma.