Abstract Nectin-4 is a type I transmembrane protein with a crucial role in calcium-independent cell-cell adhesion and a critical involvement in several signaling pathways including the PI3K/AKT and the JAK2-STAT5a pathways. Based on these interactions, Nectin-4 is involved in the regulation of migration, adhesion, and proliferation of tumor cells. In several cancer entities, unfavorable prognosis has been described for Nectin-4 positive cancers. Most of the current significance of Nectin-4 is driven by its role as a drug target for enfortumab vedotin (EV) which has been FDA approved for advanced urothelial carcinoma. EV and several other anti-Nectin-4 drugs are currently being investigated in clinical trials on bladder cancer as well as in several other tumor entities. To better comprehend the prevalence of Nectin-4 expression in different cancer types, Nectin-4 was analyzed by immunohistochemistry (IHC) on tissue microarrays (TMAs) containing 2,418 samples from 43 different tumor types. A total of 35 of 43 tumor categories showed Nectin-4 expression in at least one case, and 22 tumor categories contained at least one strongly positive case. A moderate or strong Nectin-4 positivity was most seen in basal cell carcinoma of the skin (50.0%), squamous cell carcinomas of the larynx (45.8%), vulva (44.3%), anal canal (41.0%), penis (39.0%), floor of the mouth (36.5%), skin (32.5%), pharynx (27.6%), uterine cervix (24.4%), vagina (23.3%), esophagus (20.0%), and the lung (14.5%), muscle-invasive urothelial carcinoma (39.1%), clear cell carcinoma of the ovary (33.3%), pulmonary adenocarcinoma (22.9%), endometrioid carcinoma of the ovary (17.2%), lobular carcinoma of the breast (16.7%), invasive breast carcinoma of no special type (13.3%), carcinosarcoma of the uterus (10.5%) and the ovary (6.3%), ductal adenocarcinoma of the pancreas (9.9%), mucinous carcinoma of the ovary (9.1%), gastric adenocarcinoma of diffuse (5.6%) and intestinal type (2.9%), and prostatic adenocarcinoma (2.6-4.3%). It is concluded from these data that Nectin-4 expression occurs commonly in a broad range of different cancer entities. Thus, anti-Nectin-4 cancer drugs may be applicable in multiple applications beyond bladder cancer. Citation Format: Luehr Clara, Pia Lehmke, Katharina Möller, Florian Lutz, Florian Viehweger, Georgia Makrypidi-Fraune, Martina Kluth, Claudia Hube-Magg, Nina Schraps, Fiete Gehrisch, Christian Bernreuther, Guido Sauter, Andreas H Marx, Ronald Simon, Stefan Steurer, Christoph Fraune, Viktoria Chirico, Till S. Cauditz, Bertram Veit, Clara Von Bargen, Cosima Völkel, Morton Freytag, Nathalia Gorbokon, Maximilian Lennartz, Eike C. Burandt, Anne Menz, Till Krech, Maria C. Tsourlakis, Sarah Minner. Nectin-4 expression is abundant in many different cancer entities abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7219.
Clara et al. (Fri,) studied this question.