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Nectin-4 is an adhesion protein plentiful on bladder cancer cells, used as the docking site for the ADC enfortumab vedotin.
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.
In plain words · Nectin-4 is an adhesion protein plentiful on bladder cancer cells, used as the docking site for the ADC enfortumab vedotin.
Nectin-4 is an adhesion protein plentiful on bladder cancer cells, used as the docking site for the ADC enfortumab vedotin.
Nectin-4 is a cell adhesion molecule and also a receptor for measles virus. Skin expression explains the rash seen with enfortumab.
4 products aim at Nectin-4: antibody-drug conjugates. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
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.)
Sources: Human Protein Atlas NECTIN4 tissue; Human Protein Atlas NECTIN4 pathology; Open Targets ENSG00000143217 associations
First described 2001. 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". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Nectin-4 is a cell adhesion molecule and also a receptor for measles virus. Skin expression explains the rash seen with enfortumab.
RNA: group enriched (cervix 41 nTPM, esophagus 96 nTPM, salivary gland 32 nTPM, skin 1 110 nTPM, vagina 56 nTPM), detected in many normal tissues.
No normal tissue stained high; medium in Breast, Esophagus, Oral mucosa, Skin, Tonsil, Urinary bladder.
RNA cancer enhanced: Bladder Urothelial Carcinoma 112 pTPM.
Medium only: breast cancer, cervical cancer, colorectal cancer, endometrial cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Bladder & urothelial cancer | 80-90% | IHC, moderate-strong | Wikipedia | |
| Triple-negative breast cancer | 50-60% | IHC, any expression | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
AK146D1 is Akeso's Nectin-4 × TROP2 bispecific ADC, combining the two most validated ADC addresses in one molecule.
CRB-701 is an experimental antibody-drug conjugate from Corbus Pharmaceuticals in phase 2 trials, aimed at Nectin-4.
Enfortumab vedotin is an ADC against Nectin-4 that, combined with pembrolizumab, nearly doubled survival in advanced bladder cancer.
A tiny peptide instead of an antibody carries the same payload as Padcev to Nectin-4, with far less rash and neuropathy in early data, but its developer stepped back in 2026.
Query for this target: (TITLE:"Nectin-4" OR ABSTRACT:"Nectin-4" OR TITLE:"NECTIN4" OR ABSTRACT:"NECTIN4") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Nectin-4, not a curated reading list.
Shares Aktis Oncology, Overexpression, Bispecific ADC, Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Mitosis & the spindle assembly checkpoint, Antibody-drug conjugate (ADC), Triple-negative breast cancer (TNBC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC), Triple-negative breast cancer (TNBC) and the tag adc-target.
Shares Mitosis & the spindle assembly checkpoint, Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.