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The role of belzutifan, an inhibitor of hypoxia-inducible factor, for renal cell carcinoma in adults with Von Hippel–Lindau disease: a review

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Abstract

Von Hippel–Lindau (VHL) is an autosomal dominant disease that predisposes individuals to various types of malignancies, including renal cell carcinoma, systemic hemangioblastomas, pheochromocytomas, pancreatic neuroendocrine tumors, and endolymphatic sac tumors, with renal cell carcinoma being the most prevalent. The disease is caused by a mutation in the VHL gene on chromosome 3. One function of the VHL gene is to suppress the expression of hypoxia inducible factor (HIF). HIF promotes cellular proliferation and angiogenesis under hypoxic conditions. In VHL, mutations allow HIF to promote cellular propagation unchecked, leading to neoplastic proliferation. Medications currently used for the treatment of Von Hippel Lindau associated renal cell carcinoma are tyrosine kinas inhibitors, which are enzymes downstream from HIF. These medications have been shown to have limited efficacy and an unfavorable side effect profile. Bezutifan (Welireg™) is the first drug approved by the FDA that inhibits HIF, specifically HIF2a, and has been promising for treatment of VHL-associated renal cell carcinoma. The present investigation summarizes the findings of studies conducted on the use of Belzutifan for VHL-associated renal cell carcinoma. The results to date indicate that Belzutifan is a well-tolerated and efficacious drug for VHL-associated renal cell carcinoma.

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Authors and Affiliations

  1. School of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, 71103, USA

    Anne M. Schwartz, Waddih Fakhre, Kevin Jin & Victoria E. Bollich

  2. Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, 1501 Kings Highway, Shreveport, LA, 71103, USA

    Shahab Ahmadzadeh, Sahar Shekoohi & Alan D. Kaye

  3. Department of Pharmacology, Toxicology, and Neurosciences, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, 71103, USA

    Alan D. Kaye

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  1. Anne M. Schwartz
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Correspondence to Sahar Shekoohi.

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This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

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Schwartz, A.M., Fakhre, W., Jin, K. et al. The role of belzutifan, an inhibitor of hypoxia-inducible factor, for renal cell carcinoma in adults with Von Hippel–Lindau disease: a review. Drugs Ther Perspect 39, 388–392 (2023). https://doi.org/10.1007/s40267-023-01031-y

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  • DOI: https://doi.org/10.1007/s40267-023-01031-y

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