ArticleEndocrine reviews2023
Hypoxia-Inducible Factor 2 Alpha (HIF2α) Inhibitors: Targeting Genetically Driven Tumor Hypoxia.
Article in Endocrine reviews, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
59 citing papers in PubMed, 79 citations in OpenAlex.
- Randomized phase II dose comparison LITESPARK-013 study of belzutifan in patients with advanced clear cell renal cell carcinoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2024Trial
- Cardiovascular Complications Associated with Uro-Oncology Treatments-A Primer for the Clinician.Diagnostics (Basel, Switzerland) · 2026Review
- Von Hippel-Lindau Syndrome: An Updated Narrative Review for the First-Contact Clinician.Cureus · 2026Review
- Clinicopathological and molecular determinants of pancreatic neuroendocrine tumors: toward precision risk stratification.Journal of translational medicine · 2026Review
- ATOH1 and NPAS1 are immune related prognostic biomarkers in colorectal cancer.Discover oncology · 2026Article
- Stage-resolved gene drivers of pancreatic ductal adenocarcinoma progression and therapeutic vulnerabilities.iScience · 2026Article
- Hypoxia and HIF signalling in tumour microenvironment: linking immune evasion, metabolic rewiring and epigenetic regulation.Expert reviews in molecular medicine · 2026Review
- Review
- USP10 regulates HIF2α stability by deubiquitinating HIF2α regardless ofTranslational andrology and urology · 2026Article
- Belzutifan for HIF2A-Related Pheochromocytoma and Paraganglioma: A Retrospective Study of Real-World Data.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2026Article
- Review
- Regulatory T cells in hypoxic environments.Frontiers in immunology · 2026Review
- Precision oncology in gynecologic cancers: molecular taxonomy, biomarker-guided therapeutics, and the challenge of therapeutic resistance.Frontiers in oncology · 2026Review
- Comprehensive Pan-cancer Analysis and Experimental Verification of EGLN Family: Potential Biomarkers in Cervical Cancer.Current cancer drug targets · 2026Article
- FDA fast-track approval of belzutifan is a milestone in rare cancer therapy.Nature reviews. Endocrinology · 2025Article
- Review
- Evaluating the CRP Interactome: Insights into Possible Novel Roles in Cellular Signaling and Tumorigenicity.Current issues in molecular biology · 2025Review
- Drug resistance in cancer: molecular mechanisms and emerging treatment strategies.Molecular biomedicine · 2025Review
- Comprehensive analysis of disulfidoptosis-related genes reveals molecular heterogeneity and key regulators in retinoblastoma progression.Translational pediatrics · 2025Article
- Computational investigation of Belzutifan drug delivery mechanisms using SiC nanocrystals via combined DFT and molecular dynamics approaches.Scientific reports · 2025Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Tumors driven by deficiency of the VHL gene product, which is involved in degradation of the hypoxia-inducible factor subunit 2 alpha (HIF2α), are natural candidates for targeted inhibition of this pathway. Belzutifan, a highly specific and well-tolerated HIF2α inhibitor, recently received FDA approval for the treatment of nonmetastatic renal cell carcinomas, pancreatic neuroendocrine tumors, and central nervous system hemangioblastomas from patients with von Hippel-Lindau disease, who carry VHL germline mutations. Such approval is a milestone in oncology; however, the full potential, and limitations, of HIF2α inhibition in the clinic are just starting to be explored. Here we briefly recapitulate the molecular rationale for HIF2α blockade in tumors and review available preclinical and clinical data, elaborating on mutations that might be particularly sensitive to this approach. We also outline some emerging mechanisms of intrinsic and acquired resistance to HIF2α inhibitors, including acquired mutations of the gatekeeper pocket of HIF2α and its interacting partner ARNT. Lastly, we propose that the high efficacy of belzutifan observed in tumors with genetically driven hypoxia caused by VHL mutations suggests that a focus on other mutations that similarly lead to HIF2α stabilization, such as those occurring in neuroendocrine tumors with disruptions in the tricarboxylic acid cycle (SDHA/B/C/D, FH, MDH2, IDH2), HIF hydroxylases (EGLN/PHDs), and the HIF2α-encoding gene, EPAS1, are warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.