Clear cell renal cell carcinoma (ccRCC) is closely associated with dysregulation of the VHL pathway, leading to the overexpression of HIF-2α and activation of multiple oncogenic pathways. Targeting HIF-2α with therapies such as belzutifan has provided new hope for patients with VHL syndrome and even broader applications in kidney cancer treatment. At this year’s ASCO Genitourinary Cancers Symposium (ASCO GU), Urology Frontier invited Dr. Kan Gong from Peking University First Hospital to discuss with Dr. Eric Jonasch, Director of the VHL Clinical Center at MD Anderson Cancer Center, the patient populations benefiting from belzutifan, management of adverse effects, and its future clinical applications.