HIF-2α
A master switch that kidney cancer cells leave permanently on when they lose the VHL gene; belzutifan blocks it. This dossier gathers the 1 product (1 approved), 3 trials, 6 pathways and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Biology
Transcription factor stabilised by VHL loss; drives VEGF, glycolysis, and proliferation genes.
- Clear-cell RCC
- VHL disease
- Pheochromocytoma
Elsewhere: identifiers and databases
Built from HGNC, Ensembl, UniProt and ChEMBL idsHow common it is, by cancer
Full matrix →| 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.
Products by modality and phase
Browse products →| Modality | Approved |
|---|---|
| Small molecule 1 |
Trials
Evidence ranking →| Trial | Phase | Status | Setting | Result | Products |
|---|---|---|---|---|---|
| LITESPARK-012 NCT04736706 | 3 | Negative | Untreated advanced clear-cell RCC: pembrolizumab + lenvatinib ± belzutifan (or ± quavonlimab) | Primary endpoint not met (ASCO GU 2026). | |
| LITESPARK-022 NCT05239728 | 3 | Positive | Clear-cell RCC at high risk after nephrectomy: adjuvant pembrolizumab + belzutifan vs pembrolizumab + placebo | DFS significantly improved vs pembrolizumab (interim; HR presented ASCO GU 2026). | |
| LITESPARK-005 NCT04195750 | 3 | Positive | Advanced clear-cell RCC after PD-1/PD-L1 and VEGF-TKI: belzutifan vs everolimus | PFS HR 0.75; ORR 22.7% vs 3.5%; OS not significant. |
Resistance routes that involve this target
Unaddressed routes →The resistance atlas has no route that names this target.
Pathways where it is a node
Pathway-to-drug matrix →- Nutrient competition & metabolic immunosuppressionNode: Hypoxia · 4 druggable nodes
Tumours and immune cells eat from the same plate. Cancer cells hoard glucose and glutamine, dump lactate and acid, and burn tryptophan and arginine into by-products that paralyse T cells. The tumour wins the food fight, and the immune system loses before it has fired a shot.
Which nodes have drugs → - The angiogenic switch & tumour vesselsNode: Hypoxia (HIF), RAS, p53 loss · 3 druggable nodes
A tumour cannot grow beyond a couple of millimetres without its own blood supply. The 'switch' flips when the signals calling for new vessels (VEGF, FGF, angiopoietin) outweigh the ones holding them back (thrombospondin). The vessels that result are leaky and chaotic, which starves the tumour of oxygen, blocks drugs, and gives cancer cells a way out.
Which nodes have drugs → - The pre-metastatic nicheNode: Primary tumour (hypoxic) · 3 druggable nodes
Before a single cancer cell arrives, the primary tumour sends parcels ahead: tiny vesicles (exosomes) and hormones that recruit bone-marrow cells to a distant organ and remodel it into fertile soil. By the time the seed lands, the bed is already made.
Which nodes have drugs → - Ubiquitin–proteasome system & protein homeostasisNode: Substrate (IKZF1/3, p53, HIF) · 3 druggable nodes
Cells tag unwanted proteins with a small marker called ubiquitin and feed them into a shredder, the proteasome. Myeloma cells, which make antibody in bulk, die if the shredder jams; and the newest drugs hijack the tagging machinery to make a cancer destroy its own oncoproteins.
Which nodes have drugs → - VEGF angiogenesisNode: HIF-1α / HIF-2α · 2 druggable nodes
How tumours grow their own blood supply. Low oxygen makes cells release VEGF, which tells blood-vessel cells to sprout toward the tumour.
Which nodes have drugs → - VHL / HIF oxygen sensingNode: HIF-2α · 2 druggable nodes
The VHL/HIF pathway is how cells sense oxygen (the 2019 Nobel Prize). VHL destroys HIF when oxygen is present. Kidney cancers lose VHL, so HIF-2α is permanently on and drives blood vessel growth and proliferation.
Which nodes have drugs →
Companion diagnostics and assays
Assay registry →No companion diagnostic in the registry measures this target.
Preclinical models
All models →No model entry for this target yet; check the cancer entries on the models page.
Open questions
All open questions →No open questions recorded for this target yet. Suggest one.
Ideas and companies
Key papers and the live literature
Preprints →Query 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.
Export
The dossier as machine-readable JSON: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/hif2a.json. Licence CC BY 4.0.