Nectin-4 (Poliovirus receptor-related protein 4) (Nectin-4)

Nectin-4, also known as Poliovirus receptor-related protein 4 (PVRL4), is a type I transmembrane protein belonging to the nectin family of cell adhesion molecules (UniProt Q96NY8). It is characterized by its high expression in various solid tumors, particularly urothelial (bladder) carcinoma, while maintaining limited expression in normal adult tissues (PubMed: 31851565). This differential expression pattern makes it a significant cell surface determinant and a prime target for therapeutic intervention. Biologically, Nectin-4 facilitates cell-cell adhesion and is involved in signaling pathways that drive tumor progression and metastasis (Cancer Research, 2016). The development of Enfortumab vedotin, an antibody-drug conjugate targeting Nectin-4, has revolutionized the treatment of metastatic bladder cancer by delivering potent cytotoxic agents directly to the tumor cells (FDA Label: Padcev). Beyond bladder cancer, Nectin-4 is also being investigated as a target in breast, lung, and pancreatic cancers (PubMed: 27116504).

Other names

PVRL4Poliovirus receptor-related protein 4LNIRPRR4Bladder tumor cell surface determinantNectin family member 4

Enfortumab vedotin is an antibody-drug conjugate (ADC) that binds to Nectin-4 on the cell surface. Upon binding, the ADC-receptor complex is internalized via endocytosis, followed by the release of the cytotoxic payload, monomethyl auristatin E (MMAE), through proteolytic cleavage. MMAE then binds to tubulin, inhibiting microtubule polymerization, which leads to cell cycle arrest and apoptosis (FDA Label: Padcev; PubMed: 33657448).