Figure 2.

The VHL gene is the gene for clear cell kidney cancer. The VHL protein targets hypoxia-inducible factor (HIF) for ubiquitin-mediated degradation. When the VHL gene is mutated in clear cell kidney cancer, the VHL protein cannot target and degrade HIF. HIF over-accumulates and causes increased transcription of downstream genes such as vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) (A). Current therapeutic approaches include antibodies such as bevacizumab, which target VEGF, as well as agents such as sunitinib and sorafenib, which target the VEGF and PDGF receptors.(C) Future approaches could include agents which target HIF directly.(B) From Linehan, et al.(5)