ArticleProceedings of the National Academy of Sciences of the United States of America2022
Sensitivity of
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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.
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Who cites it
30 citing papers in PubMed.
- Beyond hypoxia and ccRCC: the expanding universe of VHL novel targets and next-generation therapeutics.Biomarker research · 2026Review
- Recent advances in etiology and treatment of von Hippel-Lindau Disease (VHLD).Cancer metastasis reviews · 2026Review
- SET1B Drives Sustained HIF Activity and Disease Progression in Clear-Cell Renal Cell Carcinoma.Cancer research · 2026Article
- Lysyl oxidase drives ccRCC progression by coordinating HIF-2α transcription program with tumor microenvironment.bioRxiv : the preprint server for biology · 2026Article
- The clinical landscape of HIF2α inhibitors in oncology.Nature reviews. Clinical oncology · 2026Review
- Review
- Review
- Targeting and dissociating HIF2α from the molecular chaperone Hsp70 triggers apoptosis in kidney cancer.Communications medicine · 2026Article
- Targeting of HIF2-driven cachexia in kidney cancer.Nature medicine · 2026Article
- HIF2-driven PTHrP Causes Cachexia and Hypercalcemia in Kidney Cancer: Treatment with HIF2 Inhibitors.bioRxiv : the preprint server for biology · 2025Article
- Requirement for Cyclin D1 Underlies Cell-Autonomous HIF2 Dependence in Kidney Cancer.Cancer discovery · 2025Article
- HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy.Cell · 2025Article
- Emerging roles of metabolic biomarkers in renal cell carcinoma: from molecular mechanisms to clinical implications.Frontiers in cell and developmental biology · 2025Review
- Hypoxia-Inducible Factor in Renal Cell Carcinoma: From Molecular Insights to Targeted Therapies.Genes · 2024Review
- USP7 depletion potentiates HIF2α degradation and inhibits clear cell renal cell carcinoma progression.Cell death & disease · 2024Article
- HIF-2α expression and metabolic signaling require ACSS2 in clear cell renal cell carcinoma.The Journal of clinical investigation · 2024Article
- BMAL1-HIF2α heterodimers contribute to ccRCC.bioRxiv : the preprint server for biology · 2024Article
- Molecular analysis of primary and metastatic sites in patients with renal cell carcinoma.The Journal of clinical investigation · 2024Article
- Metabolic alterations in hereditary and sporadic renal cell carcinoma.Nature reviews. Nephrology · 2024Review
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
Inactivation of the VHL tumor suppressor gene is the signature initiating event in clear cell renal cell carcinoma (ccRCC), which is the most common form of kidney cancer. The VHL tumor suppressor protein marks hypoxia-inducible factor 1 (HIF1) and HIF2 for proteasomal degradation when oxygen is present. The inappropriate accumulation of HIF2 drives tumor formation by VHL tumor suppressor protein (pVHL)–defective ccRCC. Belzutifan, a first-in-class allosteric HIF2 inhibitor, has advanced to phase 3 testing for advanced ccRCC and is approved for ccRCCs arising in patients with VHL disease, which is caused by germline VHL mutations. HIF2 can suppress p53 function in some settings and preliminary data suggested that an intact p53 pathway, as measured by activation in response to DNA damage, was necessary for HIF2 dependence. Here, we correlated HIF2 dependence and p53 status across a broader collection of ccRCC cell lines. We also genetically manipulated p53 function in ccRCC lines that were or were not previously HIF2-dependent and then assessed their subsequent sensitivity to HIF2 ablation using CRISPR-Cas9 or the HIF2 inhibitor PT2399, which is closely related to belzutifan. From these studies, we conclude that p53 status does not dictate HIF2 dependence, at least in preclinical models, and thus is unlikely to be a useful biomarker for predicting which ccRCC patients will respond to HIF2 inhibitors.
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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.