(UroToday.com) There have been transformational changes in first-line therapy for patients with advanced renal cell carcinoma (RCC) in the past three years. Foremost among these is the move from monotherapy to combination approaches. While CheckMate 214 first brought combination therapy with dual checkpoint inhibition (nivolumab and ipilimumab) to the forefront, subsequent studies have examined combinations of immune checkpoint inhibitors and tyrosine-kinase inhibitors in the first-line setting. However, the use of combination therapy in the first-line setting has further emphasized the need to identify novel therapeutic targets. In patients with Von Hippel-Lindau (VHL) disease, aberrations of the VHL protein lead to accumulation of HIF-2α, which drives tumor growth. This contributes to clear cell renal cell carcinogenesis, as well as a number of other tumors including pancreatic neuroendocrine tumors (pNETs) and hemangioblastomas. In the Kidney and Bladder Poster session at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Dr. Ramaprasad Srinivasan presented results of an ongoing open-label phase 2 study (NCT03401788) of the HIF-2α inhibitor belzutifan in patients with VHL disease.