Nectin-4

Class

Alpha-emitting radiolabeled targeted miniprotein (Nectin-4-directed targeted alpha therapy)

Pathway

Cell-adhesion molecule overexpressed in urothelial, breast, lung, colorectal, and cervical cancers (~80-90% of urothelial cancers positive)

Nectin-4 is a cell-surface adhesion protein that helps epithelial cells stick to their neighbors and organize into tissue layers. In several cancers, particularly urothelial (bladder-lineage) cancer, tumor cells display markedly more Nectin-4 on their surface than normal tissue, making it a useful flag for identifying malignant cells even though the protein itself is not typically the driver of tumor growth. Because of this high, relatively selective surface expression, Nectin-4 has become a preferred docking point for "targeted delivery" therapies: rather than trying to block its normal adhesive function, these agents use an antibody, small molecule, or specialized miniprotein that binds Nectin-4 to guide a cytotoxic payload directly to the tumor cell. Approaches range from antibody-drug conjugates carrying chemotherapy-like payloads to radiopharmaceuticals that deliver localized radiation once bound and internalized. This strategy aims to concentrate cell-killing effects within Nectin-4-high tumor tissue while limiting exposure of tissues where the protein is absent or expressed at low levels. The broad relevance of this mechanism spans urothelial, breast, lung, colorectal, and cervical cancers, all of which can show substantial Nectin-4 overexpression, though urothelial cancer shows the highest and most consistent positivity.