ArticleTherapeutic advances in medical oncology2026
Site-specific differences in Nectin-4 expression and associated immune contexture in advanced urothelial carcinoma: implications for Nectin-4-targeted ADCs.
Article in Therapeutic advances in medical oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Nectin-4 is a key therapeutic target of antibody-drug conjugates (ADCs) in advanced urothelial carcinoma (UC), but its expression patterns and underlying biology across anatomical sites remain poorly understood. Objectives: This study aimed to elucidate Nectin-4-related features in bladder (urinary bladder carcinoma, UBC) and upper urinary tract (upper tract urothelial carcinoma, UTUC) through a multi-layered approach, including primary tumor characterization, paired primary-metastatic analyses, and immune transcriptomic profiling. Design: A retrospective cohort study. Methods: We retrospectively analyzed primary tumors from 139 patients with advanced UC, including 56 with paired metastatic specimens and 75 with sufficient primary tumor tissue for immune profiling. Membranous Nectin-4 expression was assessed by immunohistochemistry and categorized as Nectin-4 Results: Primary UBC tumors exhibited significantly higher Nectin-4 expression than UTUC tumors (median H-score 150.0 vs 95.0, Conclusion: UBC and UTUC demonstrate distinct Nectin-4 expression patterns and associated immune contexture, highlighting the biological heterogeneity of Nectin-4 in advanced UC. Further prospective studies are warranted to validate these findings and clarify their clinical implications.
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