Von Hippel-Lindau disease
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.
Pages like this
not linked directly; found by shared links- TermLi-Fraumeni syndrome (germline TP53)
Shares Hereditary cancer syndromes, Germline vs somatic mutations and the tags gap-fill, hereditary.
- ProductTemsirolimus
Shares VHL / HIF oxygen sensing, Renal cell carcinoma and the tag gap-fill.
- PersonWilliam G. Kaelin Jr.
Shares Belzutifan, VHL / HIF oxygen sensing, HIF-2α, Renal cell carcinoma.
- TermMEN1 and hereditary neuroendocrine syndromes
Shares Belzutifan, HIF-2α, Hereditary cancer syndromes, Neuroendocrine tumours.
- CancerRetinoblastoma
Shares Hereditary cancer syndromes, Germline vs somatic mutations and the tags gap-fill, hereditary.
- TargetCD73 / adenosine axis
Shares Renal cell carcinoma and the tag gap-fill.
- TechnologyPercutaneous hepatic perfusion (chemosaturation)
Shares Neuroendocrine tumours and the tag gap-fill.
- TrialLITESPARK-022
Shares Belzutifan, HIF-2α, Renal cell carcinoma.