Nectin-4
Nectin-4 is an adhesion protein plentiful on bladder cancer cells, used as the docking site for the ADC enfortumab vedotin.
Nectin-4 is highly expressed 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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · Nectin-4 is an adhesion protein plentiful on bladder cancer cells, used as the docking site for the ADC enfortumab vedotin.
- 1 · What it is
Nectin-4 is an adhesion protein plentiful on bladder cancer cells, used as the docking site for the ADC enfortumab vedotin.
- 2 · What goes wrong in cancer
Nectin-4 is a cell adhesion molecule and also a receptor for measles virus. Skin expression explains the rash seen with enfortumab.
- 3 · How drugs use it
3 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.
Biology
Nectin-4 is a cell adhesion molecule and also a receptor for measles virus. Skin expression explains the rash seen with enfortumab.
- Urothelial carcinoma (>80%)
- TNBC
- NSCLC
- Pancreatic
How common it is, by cancer
| 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.
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.
Latest papers
topQuery 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.