Nectin-4 (NECTIN4) as a Radioligand Therapy Target
Nectin-4 (NECTIN4), nectin cell adhesion molecule 4, is a cell-surface protein. In Human Protein Atlas immunohistochemistry, Nectin-4 staining is highest in bladder cancer (92% of samples positive), thyroid cancer (100% of samples positive) and ovarian cancer (100% of samples positive). Published literature suggests Nectin-4 does not readily internalize, so radionuclide retention may rely on surface binding. Clinical status: Discovery-stage (no clinical drug program).
Is Nectin-4 a good radioligand therapy target?
Scored against the six criteria that decide whether a protein can become a radioligand therapy:
- ✅ Cell-surface accessibility: Localized to the cell surface, so a radioligand can reach it from circulation.
- ✅ Tumor expression: High IHC staining in bladder cancer, 92% of samples positive.
- ❌ Internalization: Reported not to internalize.
- ⚠️ Clinical precedent: Discovery-stage (no clinical drug program)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
Nectin-4 expression in cancer
Protein expression of Nectin-4 across 20 cancer types from Human Protein Atlas immunohistochemistry. The score is a weighted staining intensity from 0 to 1; "% positive" is the share of patient samples with detectable staining.
| Cancer type | IHC score | Level | % positive |
|---|---|---|---|
| Bladder Cancer | 0.67 | High | 92% |
| Thyroid Cancer | 0.50 | Medium | 100% |
| Ovarian Cancer | 0.48 | Medium | 100% |
| Endometrial Cancer | 0.47 | Medium | 90% |
| Cervical Cancer | 0.42 | Medium | 83% |
| Skin Cancer | 0.33 | Medium | 67% |
| Colorectal Cancer | 0.30 | Medium | 80% |
| Breast Cancer | 0.28 | Medium | 75% |
| Lung Cancer | 0.28 | Medium | 58% |
| Liver Cancer | 0.27 | Medium | 70% |
| Pancreatic Cancer | 0.22 | Medium | 42% |
| Prostate Cancer | 0.15 | Low | 46% |
| Testicular Cancer | 0.15 | Low | 36% |
| Kidney Cancer | 0.11 | Low | 33% |
| Head and Neck Cancer | 0.08 | Low | 25% |
| Melanoma | 0.08 | Low | 25% |
| Neuroendocrine Tumors | 0.08 | Low | 25% |
| Glioma | 0.08 | Low | 17% |
| Gastric Cancer | 0.07 | Low | 20% |
| Lymphoma | 0.03 | Low | 9% |
Is Nectin-4 internalized?
No. Increased target antigen NECTIN4 expression is associated with reduced NECTIN4-ADC internalization, indicating that NECTIN4 does not undergo internalization upon binding.
Sources: PMID 42208541 · PMID 42167230 · PMID 42055153 · PMID 41900872 · PMID 41066596. AI-extracted from abstracts, so verify before citing.
Nectin-4 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for Nectin-4 yet. Search ClinicalTrials.gov for Nectin-4 trials.
Nectin-4 normal tissue expression
Normal-tissue expression in dose-limiting organs (kidney, liver, bone marrow, salivary glands) drives radioligand dosimetry risk. Nuclens is re-validating its normal-tissue values, so they are not shown here yet. See Nectin-4 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
Nectin-4 gene essentiality (DepMap)
CRISPR knockout effect across 1256 cancer cell lines: -0.12 (not essential). Radioligands kill by radiation, not by blocking the target, so essentiality matters less than for inhibitors. A non-essential target can still be an excellent radioligand target.
Related bladder cancer radioligand targets
EGFR · HER3 (ERBB3) · c-MET (MET) · SSTR2 · ITGAV · HER2 (ERBB2) · B7-H3 (CD276) · FAP
See all radioligand therapy targets in bladder cancer.
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Subcellular localization: UniProt via Open Targets (CC BY 4.0 / CC0). Tumor immunohistochemistry: Human Protein Atlas (CC BY-SA 4.0). Clinical trials: ClinicalTrials.gov (public domain). Gene essentiality: DepMap (CC BY 4.0). Internalization and shedding: AI-extracted from PubMed abstracts, so verify against the cited papers before relying on them. Nuclens is a first-pass triage layer, not a substitute for wet-lab validation or clinical dosimetry. Derived expression data on this page is shared under CC BY-SA 4.0.