Hypoxia-inducible factor-2α (HIF-2α) inhibitors are being investigated in ccRCC after belzutifan (Welireg®, Merck) was approved for patients with Von Hippel Lindau syndrome with RCC, CNS hemangioblastoma, and pancreatic neuroendocrine tumors based on belzutifan showing a 49% ORR of VHL patients with RCC [83]. Here, EPAS1 is linked to von Hippel-Lindau disease.