HIF-2α
A master switch that kidney cancer cells leave permanently on when they lose the VHL gene; belzutifan blocks it.
Belzutifan (Welireg) is approved in VHL disease-associated tumours, advanced RCC after immunotherapy and VEGF-TKI (LITESPARK-005), and from 2026 as adjuvant therapy with pembrolizumab in clear-cell RCC. Also approved in pheochromocytoma/paraganglioma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · A master switch that kidney cancer cells leave permanently on when they lose the VHL gene; belzutifan blocks it.
- 1 · What it is
A master switch that kidney cancer cells leave permanently on when they lose the VHL gene; belzutifan blocks it.
- 2 · What goes wrong in cancer
Transcription factor stabilised by VHL loss; drives VEGF, glycolysis, and proliferation genes.
- 3 · How drugs use it
1 product aims at HIF-2α: small molecules. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
Biology
Transcription factor stabilised by VHL loss; drives VEGF, glycolysis, and proliferation genes.
- Clear-cell RCC
- VHL disease
- Pheochromocytoma
How common it is, by cancer
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Renal cell carcinoma | 85-90% | VHL inactivation in clear-cell RCC | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Latest papers
topQuery for this target: (TITLE:"HIF-2α" OR ABSTRACT:"HIF-2α" OR TITLE:"EPAS1" OR ABSTRACT:"EPAS1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about HIF-2α, not a curated reading list.
Pages like this
not linked directly; found by shared links- IdeaBiomarker-selected adjuvant therapy in RCC (ctDNA, CAIX PET, gene signatures)
Shares LITESPARK-022, CAIX PET (89Zr-girentuximab), Belzutifan, Renal cell carcinoma.
- CompanyTelix Pharmaceuticals
Shares CAIX theranostics: 89Zr-girentuximab PET and 177Lu/225Ac-girentuximab therapy, CAIX PET (89Zr-girentuximab), Renal cell carcinoma.
- TechnologyAnti-angiogenic therapy
Shares Hallmark: inducing or accessing vasculature, Hypoxia-activated prodrugs, Angiogenesis, VEGF angiogenesis.
- TermWarburg effect
Shares VHL / HIF oxygen sensing, Nutrient competition & metabolic immunosuppression, Cancer metabolism.
- TargetVEGF / VEGFR
Shares Hallmark: inducing or accessing vasculature, Angiogenesis, The pre-metastatic niche, VHL / HIF oxygen sensing.
- TargetCSF1R
Shares The pre-metastatic niche, Nutrient competition & metabolic immunosuppression, The angiogenic switch & tumour vessels.
- ProductEverolimus
Shares LITESPARK-005, Neuroendocrine tumours, Renal cell carcinoma.
- TechnologyPartial nephrectomy, ablation & active surveillance of small renal masses