Evidence mapPaperPMID 41569310Full record

ReviewCancer chemotherapy and pharmacology2026

First-in-class HIF-2α therapy in genitourinary oncology: Belzutifan from von Hippel-Lindau disease to advanced renal cell carcinoma.

Irem Karaman, Dilek Erdem, Bulent Cetin

Abstract readReview
PubMed Publisher
In one paragraph

Review in Cancer chemotherapy and pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Irem KaramanDepartment of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
Dilek ErdemDepartment of Medicine, Division of Medical Oncology, VM Medical Park, Samsun, Turkey.
Bulent CetinDepartment of Medicine, Division of Medical Oncology, Ondokuz Mayis University Faculty of Medicine, Samsun, Turkey. caretta06@hotmail.com.ORCID http://orcid.org/0000-0001-8628-0864

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypoxia signaling governs angiogenesis, erythropoiesis, and cellular metabolism; its dysregulation via stabilized hypoxia-inducible factors (HIFs) is a shared driver across cancers. In genitourinary oncology, loss of VHL hardwires HIF-2α activity in clear-cell renal cell carcinoma (ccRCC) and across the VHL tumor spectrum. Belzutifan, which blocks HIF-2α-ARNT dimerization, is the first approved transcription-factor inhibitor in a solid tumor and the first medical therapy for a hereditary kidney-cancer syndrome (VHL). This review consolidates 2023-2025 advances: phase III validation in post-IO/TKI ccRCC (progression-free survival and response-rate gains vs. everolimus), durable first-line activity with cabozantinib, and approval for advanced pheochromocytoma/paraganglioma-including patients ≥ 12 years-extending impact to endocrine and pediatric oncology. We provide GU-focused care pathways (operate vs. treat vs. observe), pragmatic placement of belzutifan in RCC lines of therapy, and standardized monitoring for on-target anemia and hypoxia that requires coordinated oncology-hematology-pulmonology management, alongside contraception and drug-interaction counseling. Future priorities include biomarker-guided selection (HIF-2 signatures, EPAS1 variants), optimal sequencing with immunotherapy and VEGF TKIs, evaluation of triplet and peri-operative/adjuvant strategies, and development of next-generation HIF-2 inhibitors to address resistance; exploration of HIF-1 targeting and non-oncology applications (e.g., pulmonary vascular disease) is warranted. Caution is appropriate: overall survival benefit in randomized RCC trials is not yet demonstrated, resistance can emerge, and long-term hematologic and pulmonary effects require surveillance. Together, HIF-2α inhibition establishes a new, clinically actionable axis in GU oncology.

Indexed as

Antineoplastic AgentsBasic Helix-Loop-Helix ProteinsCarcinoma, Renal CellKidney Neoplasmsvon Hippel-Lindau DiseaseEndothelial PAS Domain-Containing Protein 1HumansIndenesAntineoplastic AgentsBasic Helix-Loop-Helix ProteinsbelzutifanEndothelial PAS Domain-Containing Protein 1IndenesBelzutifanHypoxia-Inducible factor 2Renal cell carcinomaVon Hippel–Lindau

Identifiers

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.