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Belzutifan for Renal Cell Carcinoma in von Hippel–Lindau Disease
Open accessAbstract
BACKGROUND: gene inactivation and constitutive activation of the transcription factor hypoxia-inducible factor 2α (HIF-2α). METHODS: In this phase 2, open-label, single-group trial, we investigated the efficacy and safety of the HIF-2α inhibitor belzutifan (MK-6482, previously called PT2977), administered orally at a dose of 120 mg daily, in patients with renal cell carcinoma associated with VHL disease. The primary end point was objective response (complete or partial response) as measured according to the Response Evaluation Criteria in Solid Tumors, version 1.1, by an independent central radiology review committee. We also assessed responses to belzutifan in patients with non-renal cell carcinoma neoplasms and the safety of belzutifan. RESULTS: After a median follow-up of 21.8 months (range, 20.2 to 30.1), the percentage of patients with renal cell carcinoma who had an objective response was 49% (95% confidence interval, 36 to 62). Responses were also observed in patients with pancreatic lesions (47 of 61 patients [77%]) and central nervous system hemangioblastomas (15 of 50 patients [30%]). Among the 16 eyes that could be evaluated in 12 patients with retinal hemangioblastomas at baseline, all (100%) were graded as showing improvement. The most common adverse events were anemia (in 90% of the patients) and fatigue (in 66%). Seven patients discontinued treatment: four patients voluntarily discontinued, one discontinued owing to a treatment-related adverse event (grade 1 dizziness), one discontinued because of disease progression as assessed by the investigator, and one patient died (of acute toxic effects of fentanyl). CONCLUSIONS: Belzutifan was associated with predominantly grade 1 and 2 adverse events and showed activity in patients with renal cell carcinomas and non-renal cell carcinoma neoplasms associated with VHL disease. (Funded by Merck Sharp and Dohme and others; MK-6482-004 ClinicalTrials.gov number, NCT03401788.).
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“PT2977/belzutifan was recently approved by the FDA for the treatment of RCC in patients with von Hippel-Lindau syndrome (47, 48).”
From HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy (2022) · cites this paper as [48]
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“The most frequent on-target toxicity with HIF-2 inhibitors (PT2385; belzutifan) is anemia from suppression of renal/hepatic erythropoietin.”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [421]
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“Anemia occurred commonly in early trials and, during prolonged belzutifan therapy, occasionally required transfusion or erythropoiesis-stimulating agents, hence the need for routine hematological monitoring [37,412,421].”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [421]
In the citing paper
“VHL gene mutations lead to the stability of HIF subunits and the constitutive activation of HIF‐mediated transcriptional pathways in patients with VHL, causing the progression of renal cell carcinoma.”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [24]
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Cites
von Hippel–Lindau disease: A clinical and scientific review
Maher, E. R., Neumann, H. P. H., & Richard, S. (2011) · European Journal of Human Genetics · doi:10.1038/ejhg.2010.175 · Cited by 744
Targeting renal cell carcinoma with a HIF-2 antagonist
Chen, W., Hill, H., Christie, A., Kim, M. S., Holloman, E., Pavia-Jimenez, A., Homayoun, F., Ma, Y., Patel, N., Yell, P., et al. (2016) · Nature · doi:10.1038/nature19796 · Cited by 709
Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo
Rankin, E. B., Biju, M. P., Liu, Q., Unger, T. L., Rha, J., Johnson, R. S., Simon, M. C., Keith, B., & Haase, V. H. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30117 · Cited by 596
Targeting the HIF2–VEGF axis in renal cell carcinoma
Choueiri, T. K., & Kaelin, W. G. (2020) · Nature Medicine · doi:10.1038/s41591-020-1093-z · Cited by 477 · cited 1×
“Upper respiratory tract infection 11 (18) 4 (7) 7 (11) 0”
On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models
Cho, H., Du, X., Rizzi, J. P., Liberzon, E., Chakraborty, A. A., Gao, W., Carvo, I., Signoretti, S., Bruick, R. K., Josey, J. A., et al. (2016) · Nature · doi:10.1038/nature19795 · Cited by 451 · cited 1×
“Alanine aminotransferase level increase 10 (16) 10 (16) 0 0”
BackgroundCourtney, K. D., Infante, J. R., Lam, E. T., Figlin, R. A., Rini, B. I., Brugarolas, J., Zojwalla, N. J., Lowe, A. M., Wang, K., Wallace, E. M., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.74.2627 · Cited by 393
Choueiri, T. K., Bauer, T. M., Papadopoulos, K. P., Plimack, E. R., Merchan, J. R., McDermott, D. F., Michaelson, M. D., Appleman, L. J., Thamake, S., Perini, R. F., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01324-7 · Cited by 305 · cited 1×
“Upper respiratory tract infection 11 (18) 4 (7) 7 (11) 0”
Self-citationPharmacologic Targeting of Hypoxia-Inducible Factors
Semenza, G. L. (2019) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010818-021637 · Cited by 288
HIF-2α regulates murine hematopoietic development in an erythropoietin-dependent manner
Scortegagna, M., Ding, K., Zhang, Q., Oktay, Y., Bennett, M. J., Bennett, M., Shelton, J. M., Richardson, J. A., Moe, O. W., & Garcia, J. A. (2004) · Blood · doi:10.1182/blood-2004-05-1695 · Cited by 237
Courtney, K. D., Ma, Y., Diaz de Leon, A., Christie, A., Xie, Z., Woolford, L., Singla, N., Joyce, A., Hill, H., Madhuranthakam, A. J., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1459 · Cited by 188
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Stephenson, K. A. J., Ling, J. Y. M., Kolawole, O. U., O’Loughlin, M., Chui, L., Gregory, C. Y., Gregory-Evans, K., Soleimani, M., & Ma, P. E. (2025) · Canadian Journal of Ophthalmology · doi:10.1016/j.jcjo.2025.08.011
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Andrés-Laguillo, M. D., García-Gónzalez, I., Rocha, S. F., Garcia-Cabero, A., Ruiz-Garcia, S., Diago-Domingo, L., Danana, A., Cussó, L., Bock, K. D., Enrı́quez, J. A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.15.675862
Luo, W., Zhao, B., & Shi, Z.-Y. (2025) · European Urology · doi:10.1016/j.eururo.2025.09.4132
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Ball, M. W., Saini, J., & Pinto, P. A. (2025) · Springer eBooks · doi:10.1007/978-3-031-97599-8_3
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Gowda, S., & Mathew, P. F. (2025) · Springer eBooks · doi:10.1007/978-3-031-97599-8_22 · Cited by 1
Xu, C., Zheng, H., Deng, Y., & Yang, L. (2025) · European Urology · doi:10.1016/j.eururo.2025.07.030
Strządała, L. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1675537
“Conversely, belzutifan ’ s success in VHL-associated tumors validates the oxygen-sensing axis as a drug target, while also highlighting that ef fi cacy can be disease-context speci fi c (16).”
Lu, Y., Yan, Z., Lyu, X., Zhang, S., & Zhao, Y. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-33885-4.00043-3
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von Werder, A. (2025) · Elsevier eBooks · doi:10.1016/b978-3-437-21184-3.00005-3
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Siclari, J. J., Favaro, D. C., Huang, R. H., & Gardner, K. H. (2025) · Protein Science · doi:10.1002/pro.70330
“…successful for identifying useful compounds — some of which led to the successful development of an FDA-approved PAS domain inhibitor targeted cancer therapeutic (Cho et al., 2016; Jonasch et al., 2021), such protein-detected NMR screening approaches can be laborious due to high sample consumption.”
Belzutifan in Von Hippel-Lindau–associated Hemangioblastomas: A Systematic Review and Meta-analysis
Yeganeh, K. J., Sargent, E. C., Ahmed, G., Klocksieben, F. A., Pressman, E., & Vakharia, K. V. (2025) · Journal of Neurological Surgery Part B Skull Base · doi:10.1055/a-2724-4297
Du, J., Manna, A. K., Medina-Serpas, M. A., Hughes, E. P., Bisoma, P., Evason, K. J., Young, A., Wilson, W. D., Brusko, T. M., Farahat, A. A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.22.683978
Sun, K., Song, L., Cui, W., Qian, C., & Liu, Q. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152933
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Rowe, I., Colombo, A., Corea, F., Pisu, F., Genova, F., Uggé, M., Ciaparrone, C., Giangrasso, A., Pipitone, G. B., Scotti, G. M., et al. (2025) · European Radiology Experimental · doi:10.1186/s41747-025-00648-0 · Cited by 1
Abimbola, A., Ayeni, A. A., Olaleye, A., Banerjee, A., & Dhanasekaran, A. K. (2025) · Cureus · doi:10.7759/cureus.97606
“On the other hand, belzutifan was reported by Jonasch et al. to have better tolerability, with most patients having grade 1-2 adverse reactions in anemia, headache, fatigue, and dizziness [12].”
EndoCompass Project: Research Roadmap for Endocrine Causes and Consequences of Cancers
Carroll, J. S., Castinetti, F., Follin, C., Luque, R. M., Stuart, A. A. V., Giwercman, A., Grozinsky‐Glasberg, S., Krausz, C. G., Paschou, S. Α., Peeters, R. P., et al. (2025) · Hormone Research in Paediatrics · doi:10.1159/000549165
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Bi, Y., Wang, R., Lu, L., Wang, L., Chen, X., Nie, X., Meng, J., & Cai, S. (2025) · Clinical and Experimental Medicine · doi:10.1007/s10238-025-01978-4 · Cited by 1
“From the first clinical human Phase I study of belzutifan (LITESPARK-004) in 2021 [93], which established its oral therapeutic dose for the treatment of patients with VHL germline mutations and limited RCC to the subsequent Phase II study (LITESPARK-013) evaluating the belzutifan efficacy in…”
Danielli, L., Rosellini, M., Tassinari, E., Marchetti, A., Mollica, V., Santoni, M., & Massari, F. (2025) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2025.2606118
“Belzutifan, a first-in-class oral HIF-2α inhibitor, was initially approved for VHL-associated RCC based on the LITESPARK-004 study, where it achieved an ORR of 64% and durable disease control [106].”
Jonasch, E., Song, Y., Freimark, J., Berman, R., Nguyen, H., Signorovitch, J., & Sundaram, M. (2024) · Figshare · doi:10.6084/m9.figshare.25237338
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Chowdhury, P., Nayak, P., Mandal, S., Das, M. K., & Tripathy, S. (2025) · Journal of the Association of Southern Urologists. · doi:10.4103/jasu.jasu_13_25
Khoury, L. Y. E., Pan, X., Hlady, R. A., Wagner, R. T., Shaikh, S., Wang, L., Humphreys, M. R., Castle, E. P., Stanton, M. L., Ho, T. H., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26585937
Khoury, L. Y. E., Pan, X., Hlady, R. A., Wagner, R. T., Shaikh, S., Wang, L., Humphreys, M. R., Castle, E. P., Stanton, M. L., Ho, T. H., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26585934
Chen, R., Wu, J. T., Che, Y., Jiao, Y., Sun, H., Zhao, Y., Chen, P., Meng, L., & Zhao, T. (2024) · Figshare · doi:10.6084/m9.figshare.26694192
Tucci, F., Drydale, E., Bancroft, J. M., Amin, S., Pernes, J. I., Gardumi, G., Kanyowa, T., Lima, M., Nasreddin, N., Lombardi, O., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.19.695541
Kawai, J., Fukada, M., Mitsui, N., Horaguchi, T., Yasufuku, I., Tajima, J. Y., Kiyama, S., Tanaka, Y., Murase, K., & Matsuhashi, N. (2025) · 日本消化器外科学会雑誌 · doi:10.5833/jjgs.2025.0001
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Fouad, M. A., Parry, C. S., Miller, S. A., Malhotra, S., Doyle, G. A. R., Shimabenga, E., Nurilloeva, M., Bondarenko, E., Andrianov, G. V., Childers, W., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.02.697373
Greco, F., Panunzio, A., Vescovo, M., Perillo, G., Bernetti, C., Tafuri, A., Carotti, S., Zobel, B. B., & Mallio, C. A. (2026) · ONCOLOGIE · doi:10.1515/oncologie-2025-0443
“Belzutifan is an HIF-2 α inhibitor and represents a therapeutic option for advanced ccRCC, especially in tumors that show alterations in cellular oxygenation or stress response pathways [55], potentially related to AUP1 expression.”
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Kilani, A., Assaf, A., Jochem, C., Vogt, D., Laible, M., Parlak, M., & Wolf, A. (2026) · Research Square · doi:10.21203/rs.3.rs-8503671/v1
Krishnan, A., Baviskar, Y., Chatterjee, A., Dasgupta, A., Epari, S., Sahu, A., Chinnaswamy, G., Menon, N. S., Moiyadi, A. V., Gupta, T., et al. (2026) · Cancer Medicine · doi:10.1002/cam4.71483
Melzer, M. K., Mattigk, A., Gaidzik, V. I., Gaisa, N. T., Schwenke, J., & Zengerling, F. (2026) · Urology Case Reports · doi:10.1016/j.eucr.2026.103376
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Ganser, A., Hertenstein, B., & Ludwig, W. (2026) · Springer eBooks · doi:10.1007/978-3-662-72738-6_5
Huỳnh, Q. H., Nguyen, C. P., Nguyen, X. Q., Thi, M. K. T., & Nguyen, S. B. (2026) · Journal of Surgical Case Reports · doi:10.1093/jscr/rjag092
“Targeted systemic options such as the HIF-2 α inhibitor belzutifan may reduce the need for repeated interventions in selected VHL-associated neoplasms [10].”
Zheng, Y., Du, Y., Ma, Z., Luo, Y., Lu, J., & Shang, P. (2026) · Cancers · doi:10.3390/cancers18050768
“Although vascular endothelial growth factor (VEGF) pathway inhibitors and immune checkpoint blockade have improved survival in some patients, response rates remain limited and tumor heterogeneity contributes to therapeutic resistance and disease progression [7–9].”
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“Its inactivation leads to the constitutive stabilization and accumulation of HIF2 a , even at normal oxygen levels (32).”
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Jena, R. S., & Mishra, A. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1815377
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“Furthermore, in the pivotal clinical trial of belzutifan for the treatment of VHL-RCC, 82% of patients with VHL-RCC also had VHL-CNS-Hb during the baseline period [13].”
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Deng, D., Feng, H., Fendler, A., Dovga, Y., Byrne, F., Spencer, C., Martin, A. C., Fernández-Sanromán, Á., Bouricha, O., Shepherd, S. T. C., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.30.721837
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“Additionally, specific systemic treatments for specific forms of hRCC become available [ 9 , 10 ].”
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“These findings provide a framework for understanding belzutifan’s clinical indications and ongoing development, with completed RCC trials summarized in Table 1 [4,9,23,27,29,35-39], and active trials across various tumors are outlined in Tables 2 - 3 .”
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“To inhibit HIF-2A activity, we treated these cells with increasing doses of belzutifan/PT2977 ( 33 , 34 ).”
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Fu, J., He, Y., Lu, J., Wei, H., Sun, W., Geng, J., Liu, K., Liu, J. J., Liu, Z., Wang, K., et al. (2026) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.6c00152
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Peng, Y., Che, Y., Zhao, Y., Wang, Z., Pei, Z., Hu, Y., Yin, Y., Pan, X., Hu, X., Wei, M., et al. (2026) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2026.06.040
Erdem, S., AMPARORE, D., Re, C., Verep, S., Umberto Capitanio, A., Larcher, A., Roussel, E., Klatte, T., Bertolo, R., Muselaers, S., et al. (2026) · World Journal of Urology · doi:10.1007/s00345-026-06562-3
“It was approved based on a phase II, open-label, single-arm study (LITESPARK-004) [76, 77].”
Qin, G., Yu, H., Zhao, Y., Xia, W., Qin, Y., Liang, X., Chen, T., Li, Y., Zou, T., Liu, J., et al. (2026) · Molecular Cell · doi:10.1016/j.molcel.2026.06.022
Alcoreza, A. A. D., Song, C., & Lee, J. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1870341
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Wu, X.-H., Zheng, W., Xu, W.-T., Chen, C.-R., Jin, X.-P., Lin, F., Zheng, Q., Wei, Y., Chen, S., Xu, N., et al. (2026) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2026.112262
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Takeuchi, K., Okamoto, T., Sekine, Y., Shinohara, M., Tamaki, G., Abe, N., Kobayashi, S., Fujita, N., Sato, S., Habuchi, T., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-10294805/v1
Multidisciplinary Treatment of Hemangioblastoma and Recent Topics
Takayanagi, S., & Saito, N. (2025) · Japanese Journal of Neurosurgery · doi:10.7887/jcns.34.450
Therapeutic Targets for Hepatic Fibrosis Driven by Hypoxia-Mediated Hepatic Stellate Cell Activation
Li, W., Li, T., & Mao, J. (2026) · Biomolecules · doi:10.3390/biom16081089
“Belzutifan is the first FDA-approved HIF-2 α -selective inhibitor for the treatment of VHL disease-associated renal cell carcinoma [53].”
Wang, Y., Malkin, D. M., & Lipkin, S. M. (2026) · International Journal of Cancer · doi:10.1002/ijc.70674
Zhang, Y., Liu, F., Cao, X., Guo, D., Zhu, Y., & Sun, H. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1880422
“Clinical trial data have reported objective response rates of 67% for renal cell carcinoma, 91% for pancreatic neuroendocrine tumors, and 48% for central nervous system hemangioblastomas (15, 16).”
Patel, K., Jahanzeb, M., Boccia, R., Olson, N., Nadkarni, R., Naidu, D., Kodali, A., Clinton, N., Lozano, R., Anandpura, N., et al. (2026) · NCODA Oncology and Hematology Meeting Abstracts · doi:10.67209/yngr8908
Michael, P. D., Loebach, L., Blachman-Braun, R., Fu, H., Millan, B., Saini, J., Gurram, S., Linehan, W. M., & Ball, M. W. (2026) · Current Oncology · doi:10.3390/curroncol33080468
“The recent approval of belzutifan, a HIF-2 α inhibitor, for VHL disease-associated renal cell carcinoma represents a paradigm shift that may reduce the need for surgical interventions, including completion nephrectomy, in select patients [21,22,25].”
Self-citationRenal cell carcinoma: Molecular mechanisms and emerging therapeutic strategies
Vaghela, A. R., Dulera, M., & Marakana, D. (2026) · World Advances in Renal Medicine · doi:10.25259/warm_19_2025
Jiménez, C., Waguespack, S. G., Kaplan, J., Habra, M. A., & Varghese, J. M. (2026) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgag324
Ferrara, A. M. (2026) · L Endocrinologo · doi:10.1007/s40619-026-01865-4
“Il ruolo del belzutifan e dei farmaci innovativi nella VHL [11, 12], sarà approfondito e trattato in questo stesso numero de L’Endocrinologo nella rubrica Farmaci Innovativi in Endocrinologia.”
Cryptic small-molecule binding sites in the ARID1B DNA-binding domain
Carbone, C. E., Schönherr, H., Zhao, V. Y., Pierce, L., He, J., Shortsleeves, K., Babik, S., Venter, P. A., Krueger, E. B., Fortin, P. D., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2529603123
Belzutifan nella malattia di von Hippel-Lindau: il primo inibitore di HIF-2$\alpha $
Ferrara, A. M. (2026) · L Endocrinologo · doi:10.1007/s40619-026-01868-1
“L’anemia rappresenta la tossicità on-target più frequente, in relazione alla soppressione dell’asse HIF-2 α /EPO [1, 2].”
InfluentialRecent advances in etiology and treatment of von Hippel-Lindau Disease (VHLD)
Pirestani, S., Nicolas, É., Broadrup, R. L., Clapper, M. L., & Golemis, E. A. (2026) · Cancer and Metastasis Reviews · doi:10.1007/s10555-026-10370-x
“The first-in-class compound belzutifan (also known as MK-6482 and previously designated PT2977) was approved by the FDA for VHLD based on results from a phase II trial assessing drug efficacy in VHLD patients with ccRCC [38].”
Hu, Y., Zhao, X., Xu, Q., Wang, N., Zhao, X., Wang, Y., Cao, H., Gu, Y., Yan, L., Teng, L., et al. (2026) · Cellular Signalling · doi:10.1016/j.cellsig.2026.112819
Rare genetic endocrine tumor syndromes: VHL, NF1, TSC, and Carney complex
Vrachnis, D. N., & Stratakis, C. A. (2026) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2026.102159
Clinical outcomes of HIF-2 α inhibition in Von Hippel–Lindau disease: a multicenter real-world study
Abbas, M. A., Zarka, J. G., Silva, A. C., Cingolani, F., Sarfraz, M. U., Jang, A., Khan, M. A., Nahhat, F., Tan, W., Costello, B. A., et al. (2026) · The Oncologist · doi:10.1093/oncolo/oyag331
Kopinski, P. K., Duffner, S. J., & Anguita, R. (2026) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2026.102162
Contemporary pharmacological management of anemia associated with chronic kidney disease
Saito, T., Nangaku, M., & Mimura, I. (2026) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2026.2726516
“In parallel with growing interest in the development of anticancer agents targeting the HIF pathway, belzutifan, a HIF-2α inhibitor, has demonstrated efficacy in von Hippel–Lindau disease-associated renal cell carcinoma and has already entered clinical practice [95].”
Renal cell carcinoma: molecular understanding and therapeutic development
Hou, T., Hua, X., Wei Min, N. I., Yan, P., Inuzuka, H., & Wei, W. (2026) · Cell Death and Differentiation · doi:10.1038/s41418-026-01857-9
Renal Cell Carcinoma in the Geriatric Population: Toward a Frailty-Adapted Therapeutic Paradigm
Özsürekçi, C., Yazar, U., & Açıkgöz, Y. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15176726
“Clinical trials have reported anemia in the majority of treated patients, with grade ≥ 3 anemia occurring frequently enough to necessitate dose interruptions, erythropoiesis-stimulating agents, or blood transfusions in a substantial subset of patients [108,111].”
Luo, C., Li, T., Tak, J., DeBerge, M., Tsai, K., & Eltzschig, H. K. (2026) · Nature Reviews Cardiology · doi:10.1038/s41569-026-01339-y
Liu, B., & Liao, Y. (2026) · Journal of Biosciences and Medicines · doi:10.4236/jbm.2026.149006
Ying, F., Fan, L., Zhu, X., Hong, B., Song, X., Zhang, T., & Sun, M. (2026) · Letters in Drug Design & Discovery · doi:10.1016/j.lddd.2026.100563
Msaouel, P., Rosa, S. L., Abel, E. J., Albiges, L. K., Barata, P. C., Berg, S. A., Braun, D. A., Brugarolas, J., Campbell, M. T., Carlo, M. I., et al. (2026) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2026.07.035
Self-citationKilani, A., Assaf, A., Jochem, C., Vogt, D., Laible, M., Parlak, M., Alkabouni, W., & Wolf, A. (2026) · International Journal of Retina and Vitreous · doi:10.1186/s40942-026-00932-0
“…is a rare autosomal-dominant tumor syndrome caused by pathogenic variants in the VHL tumor suppressor gene, resulting in constitutive activation of hypoxia-inducible factor (HIF) signaling and the development of highly vascular neoplasms across multiple organ systems, including the retina [1–4].”
Yang, D., Sun, Y., & Zhang, S. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1922111
Von Hippel-Lindau syndrome presenting as a lateral ventricular space-occupying lesion: a case report
Liu, L., Chen, Y., Zhang, Z., & Zhou, G. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1899311
“The phase 2 LITESPARK-004 trial demonstrated meaningful antitumour activity across all three tumor types, including CNS hemangioblastomas, bringing a revolutionary change in disease management (6).”
Adamski, W. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27188244
“…orbital alpelisib case series, n = 5 treated [73] Phase II [154,185] Anemia ~90%, hypoxia, fatigue (systemic); no direct ocular toxicity reported [154] 1—single-arm phase 2, 16/16 evaluable eyes in 12 participants improved, no comparator [154,155] https://doi.org/10.3390/ijms27188244 None…”
InfluentialEmerging patterns of kidney cancer in young adults: where do we stand?
Troisi, P., Occhipinti, D., Ligato, C., Sardaro, V., Campi, R., Merenda, E., Cappoli, N., Arduini, D., Messina, G., Leo, D. D., et al. (2026) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2026.105607
Dual hypoxia-inducible factor-1/2 inhibition: A new frontier in hypoxia-directed cancer therapy
Xue, E. (2026) · Annals of Oncology Research and Therapy · doi:10.4103/aort.aort_40_26
Li, J., Liu, S., Fu, L., Bo, Q., Bai, Y., & Dai, X. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1960932
“A single-group study reported activity in VHL disease-associated renal-cell carcinoma (Jonasch et al., 2021).”
Metadata
- Authors
- Jonasch, E., Donskov, F., Iliopoulos, O., Rathmell, W. K., Narayan, V. K., Maughan, B. L., Oudard, S., Else, T., Maranchie, J. K., Welsh, S. J., Thamake, S., Park, E. K., Perini, R. F., Linehan, W. M., & Srinivasan, R.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- From the University of Texas M.D. Anderson Cancer Center, Houston (E.J.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (O.I.); Vanderbilt University Medical Center, Nashville (W.K.R.); University of Pennsylvania, Philadelphia (V.K.N.); the University of Utah, Salt Lake City (B.L.M.); Hôpital Européen Georges-Pompidou, University of Paris, Paris (S.O.); the University of Michigan, Ann Arbor (T.E.); the University of Pittsburgh, Pittsburgh (J.K.M.); Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom (S.J.W.); Merck, Kenilworth, NJ (S.T., E.K.P., R.F.P.); and the Center for Cancer Research, National Cancer Institute, Bethesda, MD (W.M.L., R.S.).
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2021-11-25
- Volume
- 385
- Issue
- 22
- Pages
- 2036-2046
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC9275515
- OpenAlex
- W3215189579
- Cited by
- 714
- References
- 22
- Citations by year
- 2026: 140 · 2025: 167 · 2024: 135 · 2023: 140 · 2022: 128 · 2021: 4
- FWCI
- 66.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA
- Topics
- Health Sciences › Medicine › Oncology › Renal cell carcinoma treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Ear and Head Tumors
- Keywords
- belzutifan, HIF-2α inhibition, von Hippel-Lindau disease, renal cell carcinoma, hemangioblastoma, retinal hemangioblastoma, pancreatic lesions, anemia, drug safety, objective response
- MeSH terms
- Adult, Aged, Anemia, Antineoplastic Agents, Carcinoma, Renal Cell, Fatigue, Female, Follow-Up Studies, von Hippel-Lindau Disease, Humans, Indenes, Kidney Neoplasms, Male, Middle Aged, Neoplasms, Multiple Primary, Pancreatic Neoplasms, Age of Onset, Hemangioblastoma, Neuroendocrine Tumors, Disease Progression, Basic Helix-Loop-Helix Proteins
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