biostudies-literatureHasanov ENCI NIH HHS495-504https://www.ebi.ac.uk/biostudies/studies/S-EPMC8268068biostudies-literatureUnknown30(5)<h4>Introduction</h4>Von Hippel-Lindau (VHL) disease is an inherited autosomal dominant syndrome caused by a germline mutation and/or deletion of the <i>VHL</i> gene. Inappropriate hypoxia-inducible factor (HIF)-mediated transcription of proangiogenic and metabolic genes leads to the development of tumors and cysts in multiple organs. Surgery is a standard treatment for localized tumors with a risk of metastasis or organ dysfunction. Repeated surgeries cause substantial morbidity and have a major impact on quality of life. There is an urgent need to develop effective and safe systemic treatments for VHL disease manifestations. The small-molecule HIF 2 alpha inhibitor MK-6482 (belzutifan) has demonstrated significant efficacy in VHL disease related renal cell carcinomas, hemangioblastomas, Expert opinion on investigational drugsMK-6482 as a potential treatment for von Hippel-Lindau disease-associated clear cell renal cell carcinoma.PMC8268068P30 CA016672Jonasch EHasanov EfalseMK-6482 as a potential treatment for von Hippel-Lindau disease-associated clear cell renal cell carcinoma.<h4>Introduction</h4>Von Hippel-Lindau (VHL) disease is an inherited autosomal dominant syndrome caused by a germline mutation and/or deletion of the <i>VHL</i> gene. Inappropriate hypoxia-inducible factor (HIF)-mediated transcription of proangiogenic and metabolic genes leads to the development of tumors and cysts in multiple organs. Surgery is a standard treatment for localized tumors with a risk of metastasis or organ dysfunction. Repeated surgeries cause substantial morbidity and have a major impact on quality of life. There is an urgent need to develop effective and safe systemic treatments for VHL disease manifestations. The small-molecule HIF 2 alpha inhibitor MK-6482 (belzutifan) has demonstrated significant efficacy in VHL disease related renal cell carcinomas, hemangioblastomas, 2021-01-01T00:00:00Z2021 May2025-04-25T16:53:07.072Z2025-02-18T23:32:14.308ZS-EPMC82680683394536610.1080/13543784.2021.1925248