Loading
Von Hippel-Lindau disease is an inherited condition causing kidney cancers, adrenal tumours, and blood-vessel tumours of the brain, spine, eye and pancreas from early adulthood. It taught us how cells sense oxygen and gave rise to the drug belzutifan, the first medicine for VHL tumours.
Germline VHL mutation (1 in 36,000) leads to loss of the VHL protein, stabilisation of HIF-2α and tumours: clear-cell RCC (~70% lifetime, multiple and bilateral), retinal and CNS haemangioblastomas, phaeochromocytoma, pancreatic NETs and cysts, endolymphatic sac tumours. Management was serial surveillance and repeated organ-sparing surgery (renal tumours resected at 3 cm). Belzutifan (HIF-2α inhibitor; Study 004: 49% RCC response) was approved in 2021 for VHL-associated RCC, CNS haemangioblastoma and pNET not requiring immediate surgery, reducing surgeries. VHL biology underpins the 2019 Nobel Prize (Kaelin, Ratcliffe, Semenza) and the whole HIF-2α programme in sporadic RCC.
Shares Hereditary cancer syndromes, Germline vs somatic mutations and the tag hereditary.
Shares VHL / HIF oxygen sensing, HIF-2α, Belzutifan, Renal cell carcinoma.
Shares HIF-2α, Belzutifan, Hereditary cancer syndromes, Neuroendocrine tumours.
Shares VHL / HIF oxygen sensing, HIF-2α, Belzutifan, Renal cell carcinoma.
Shares HIF-2α, Belzutifan, Renal cell carcinoma.
Shares Hereditary cancer syndromes, Germline vs somatic mutations, Neuroendocrine tumours and the tag hereditary.
Shares Hereditary cancer syndromes, Germline vs somatic mutations and the tag hereditary.
Shares HIF-2α, Belzutifan, Renal cell carcinoma.