(UroToday.com) Enfortumab vedotin is an antibody-drug conjugate targeting Nectin-4 (encoded by the PVRL4/NECTIN4 gene) approved for treatment-refractory metastatic urothelial cancer based on several studies.1-3 EV-201 represented a heavily pre-treated population with a 44% overall response rate, 12% complete response rate, 7.6-month median duration of response, 11.7-month median overall survival, and 5.8-month progression-free survival.2 However, factors that mediate sensitivity or resistance to enfortumab vedotin are unknown. At the 2021 GU ASCO annual meeting, Dr. Carissa Chu and colleagues assessed the heterogeneity in Nectin-4 expression across molecular subtypes of urothelial cancer to assess the impact on sensitivity to enfortumab vedotin. The hypothesis of this study was that Nectin-4 expression is variable across molecular subtypes of bladder cancer and mediates sensitivity to enfortumab vedotin.