Clinical trials involving patients with VHL disease and unresectable HBs have historically explored the use of tyrosine kinase inhibitors (targeting genes from the VEGFR, PDGFR, and EGFR families, which are regulated by the HIF pathway), such as semaxanib, vatalanib, sunitinib, and pazopanib, as well as monoclonal anti-VEGF antibodies (bevacizumab). This evidence concerns the gene KDR and von Hippel-Lindau disease.