{"entity":{"id":"nectin4","kind":"target","name":"Nectin-4","aka":[],"tldr":"Nectin-4 is an adhesion protein plentiful on bladder cancer cells, used as the docking site for the ADC enfortumab vedotin.","summary":"Nectin-4 is expressed at high levels in urothelial carcinoma and also in breast, lung, and pancreatic cancers. Enfortumab vedotin plus pembrolizumab is first-line standard in advanced urothelial cancer (EV-302). Next-generation Nectin-4 ADCs with topoisomerase-I payloads (MK-3120) and Nectin-4×TROP2 bispecific ADCs (AK146D1, AVZO-103) are in development.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Nectin-4","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Nectin-4"}],"tags":["adc-target"],"related":["nectin-4-expression"],"cancers":["urothelial","tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":["crb-701"],"companies":["emergence-therapeutics","marengo-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":["nct07299747"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"NECTIN4","role":[],"sources":[],"specificity":"tumour-associated","distribution":"few-types","specificityNote":"Tumour-associated overexpression: 4 cell-killing or cell-finding medicines (CRB-701, AK146D1, Enfortumab vedotin and more) aim at the antigen, which HPA finds with no normal tissue stained high; the medicine relies on the tumour carrying more of it than the normal tissue it shares it with. HPA NECTIN4: RNA group enriched (cervix 41 nTPM, esophagus 96 nTPM, salivary gland 32 nTPM); no normal tissue stained high; highest cancer staining urothelial cancer (3 of 12 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Bladder & urothelial cancer, Breast cancer (all types)); Open Targets associates it with 1 specific cancer type at or above 0.5 (urothelial carcinoma). (Rule 5 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas NECTIN4 tissue","url":"https://www.proteinatlas.org/ENSG00000143217-NECTIN4/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas NECTIN4 pathology","url":"https://www.proteinatlas.org/ENSG00000143217-NECTIN4/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000143217 associations","url":"https://platform.opentargets.org/target/ENSG00000143217/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:19688","ensembl":"ENSG00000143217","uniprot":"Q96NY8","entrez":"81607","firstDescribed":2001,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Reymond et al, J. Biol. Chem, 2001, \"Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through V domain interaction\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/11544254/","biology":"Nectin-4 is a cell adhesion molecule and also a receptor for measles virus. Skin expression explains the rash seen with enfortumab.","whereFound":["Urothelial carcinoma (>80%)","TNBC","NSCLC","Pancreatic"],"targetClass":"surface-antigen","prevalence":[{"cancerId":"urothelial","pct":"80-90","measure":"IHC, moderate-strong","source":"https://en.wikipedia.org/wiki/Nectin-4"},{"cancerId":"tnbc","pct":"50-60","measure":"IHC, any expression","source":"https://en.wikipedia.org/wiki/Nectin-4"}]},"route":"/targets/nectin4/","neighbours":{"biomarker":[{"id":"nectin-4-expression","kind":"biomarker","name":"Nectin-4 expression","route":"/biomarkers/nectin-4-expression/"}],"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"},{"id":"urethral","kind":"cancer","name":"Urethral cancer","route":"/cancers/urethral/"},{"id":"urethral-urothelial-carcinoma","kind":"cancer","name":"Urothelial carcinoma of the urethra","route":"/cancers/urethral-urothelial-carcinoma/"}],"drug":[{"id":"ak146d1","kind":"drug","name":"AK146D1","route":"/drugs/ak146d1/"},{"id":"crb-701","kind":"drug","name":"CRB-701","route":"/drugs/crb-701/"},{"id":"enfortumab-vedotin","kind":"drug","name":"Enfortumab vedotin","route":"/drugs/enfortumab-vedotin/"},{"id":"zelenectide-pevedotin","kind":"drug","name":"Zelenectide pevedotin","route":"/drugs/zelenectide-pevedotin/"}],"company":[{"id":"aktis-oncology","kind":"company","name":"Aktis Oncology","route":"/companies/aktis-oncology/"},{"id":"avenzo","kind":"company","name":"Avenzo Therapeutics","route":"/companies/avenzo/"},{"id":"emergence-therapeutics","kind":"company","name":"Emergence Therapeutics","route":"/companies/emergence-therapeutics/"},{"id":"marengo-therapeutics","kind":"company","name":"Marengo Therapeutics","route":"/companies/marengo-therapeutics/"}],"trial":[{"id":"nct07299747","kind":"trial","name":"Clinical Trial of VBC103 in Patients With Advanced Malignant Solid Tumors","route":"/trials/nct07299747/"},{"id":"ev-302","kind":"trial","name":"EV-302 / KEYNOTE-A39","route":"/trials/ev-302/"},{"id":"ev-303","kind":"trial","name":"EV-303 / KEYNOTE-905","route":"/trials/ev-303/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"bispecific-adc","kind":"technology","name":"Bispecific ADC","route":"/technologies/bispecific-adc/"},{"id":"peptide-drug-conjugate","kind":"technology","name":"Peptide-drug & small-molecule-drug conjugates","route":"/technologies/peptide-drug-conjugate/"}],"person":[{"id":"jonathan-rosenberg","kind":"person","name":"Jonathan E. Rosenberg","route":"/people/jonathan-rosenberg/"},{"id":"thomas-powles","kind":"person","name":"Thomas Powles","route":"/people/thomas-powles/"}],"paper":[{"id":"paper-ev-302-nejm-2024","kind":"paper","name":"EV-302: enfortumab vedotin plus pembrolizumab replaces chemotherapy as first treatment for advanced bladder cancer","route":"/key-papers/paper-ev-302-nejm-2024/"}],"term":[{"id":"overexpression","kind":"term","name":"Overexpression","route":"/terms/overexpression/"}],"pathway":[{"id":"mitotic-spindle-checkpoint","kind":"pathway","name":"Mitosis & the spindle assembly checkpoint","route":"/pathways/mitotic-spindle-checkpoint/"}]}}