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

Nectin-4, also known as Poliovirus receptor-related protein 4 (PVRL4), is a type I transmembrane glycoprotein belonging to the nectin family of cell adhesion molecules (UniProt: Q96NY8). It plays a critical role in the formation and maintenance of adherens junctions by interacting with other nectins and cadherins, thereby facilitating cell-cell signaling and structural integrity (PubMed: 11544254). While its expression is limited in healthy adult tissues—primarily found in the placenta—it is significantly overexpressed in various solid tumors, including urothelial, breast, lung, and ovarian cancers (PubMed: 21856768). This differential expression makes Nectin-4 an ideal therapeutic target, particularly for antibody-drug conjugates (ADCs) like enfortumab vedotin, which delivers a cytotoxic payload directly to malignant cells (FDA: Padcev Label). Beyond its role in oncology, mutations in the PVRL4 gene are associated with ectodermal dysplasia-syndactyly syndrome, highlighting its importance in developmental morphogenesis (PubMed: 20705278). Current clinical research focuses on expanding the use of Nectin-4 targeted therapies and managing associated toxicities such as skin reactions and neuropathy (ClinicalTrials.gov: NCT03223116).

Other names

PVRL4LNIRPRR4EDSS1Nectin cell adhesion molecule 4

Antibody-drug conjugate (ADC) targeting and internalization followed by the intracellular release of cytotoxic agents (e.g., monomethyl auristatin E) to induce cell death.