[Belzutifan in the treatment of renal cell carcinoma]

As the first approved inhibitor of hypoxia-inducible factor 2 alpha (HIF-2α), belzutifan represents a significant advancement in the treatment of clear cell renal cell carcinoma. By directly blocking the transcription factor it interrupts the oncogenic cascade initiated by the loss of the von Hippel-Lindau (VHL) protein. The current approval includes monotherapy in the third-line setting as well as VHL-associated tumors; however, recent data from the LITESPARK studies suggest a possible expansion into second-line and adjuvant settings. The side effect profile is characterized by specific on-target effects, such as anemia and hypoxia, which require close monitoring.