Targeting HIF-2α and anemia: A therapeutic breakthrough for clear-cell renal cell carcinoma
•Recent research in RCC pathogenesis has emphasized its heterogeneity, with a focus on the VHL gene's critical role in oxygen sensing and the subsequent dysregulation of HIF complexes. This deeper understanding of the VHL pathway's role in RCC development holds promise for targeted therapi...
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Veröffentlicht in: | Cancer treatment reviews 2024-09, Vol.129, p.102801, Article 102801 |
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Sprache: | eng |
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Zusammenfassung: | •Recent research in RCC pathogenesis has emphasized its heterogeneity, with a focus on the VHL gene's critical role in oxygen sensing and the subsequent dysregulation of HIF complexes. This deeper understanding of the VHL pathway's role in RCC development holds promise for targeted therapies.•The development and clinical evaluation of belzutifan, has demonstrated promising outcomes in patients with advanced RCC. This highlights the potential for targeted therapies that address the underlying molecular mechanisms of RCC.•The regulation of EPO production by belzutifan and its downstream effects on erythropoiesis underscore the interconnectedness of molecular pathways in RCC.•Clinicians managing patients with belzutifan therapy must navigate various considerations, including addressing belzutifan-induced anemia. Continued research is necessary to optimize treatment protocols and improve patient outcomes.
Renal cell carcinoma (RCC) is a heterogenous disease which the incidence is increasing worldwide. The identification and understanding of the role of the Von Hipple Lindau (VHP) in regulating the hypoxia-inducible factor signaling pathway has revolutionized the treatment of this disease. Belzutifan is an oral hypoxia-inducible factor (HIF)-2α inhibitor, which has demonstrated efficacy in treating von Hippel-Lindau (VHL) disease and for the treatment of adults with RCC who experienced disease progression after PD-1/PD-L1– and VEGFR-targeted therapies. One of the most common adverse effect of this drug is anemia; however, it is treatment is not well known. This review summarizes role of the VHL-HIF pathway in ccRCC aroused the interest of targeting HIF activity, the history of belzutifan development and their relationship to anemia as well as propose a management algorithm. |
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ISSN: | 0305-7372 1532-1967 1532-1967 |
DOI: | 10.1016/j.ctrv.2024.102801 |