Nectin-4 expression is abundant in many different cancer entities

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.