Belzutifan (MK-6482): Biology and Clinical Development in Solid Tumors
Document Type
Journal Article
Publication Date
2-1-2023
Journal
Current oncology reports
Volume
25
Issue
2
DOI
10.1007/s11912-022-01354-5
Keywords
Belzutifan; HIF-2a; VHL; ccRCC
Abstract
PURPOSE OF REVIEW: To review the biology, drug development, and clinical data regarding the efficacy and safety of belzutifan (MK-6482), a small molecule inhibitor of HIF-2α. RECENT FINDINGS: Belzutifan, a second-generation HIF-2α inhibitor, was shown to provide clinically meaningful benefit in the treatment of VHL-associated tumors (including ccRCC, pancreatic lesions as well as neuroendocrine tumor, and CNS hemangioblastomas). The recommended dose of belzutifan is 120 mg orally daily and half-life is 14 h. In pretreated ccRCC, belzutifan achieved disease control rate of 80% in phase I trial. The most common side effects include anemia and hypoxia related symptoms. Investigation into the important role HIF-2α plays in the expression of genes associated with angiogenesis, erythropoiesis, carcinogenesis, and progression of tumors and the discovery of structural vulnerability within HIF-2α have resulted in the development of a new therapy that has demonstrated efficacy and safety in recent clinical trials. Further research is ongoing to optimize therapeutic benefits from this new exciting therapeutic modality and to improve the outcome of HIF-2α-driven tumors.
APA Citation
Choi, WonSeok W.; Boland, Julia L.; Kalola, Akshar; and Lin, Jianqing, "Belzutifan (MK-6482): Biology and Clinical Development in Solid Tumors" (2023). GW Authored Works. Paper 2214.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2214
Department
Medicine