Radioligand Therapy Targets in Bladder Cancer
We screened every cell-surface protein with tumor immunohistochemistry data in bladder cancer (including urothelial carcinoma). 4,316 show detectable protein staining. Established and emerging radioligand targets expressed in bladder cancer include HER3 (ERBB3), ITGAV, EGFR and Nectin-4 (NECTIN4). Below, we rank every candidate by tumor expression, internalization and clinical maturity.
Established and emerging radioligand targets in bladder cancer
Targets already pursued with radioligands or other targeted modalities that show protein expression in bladder cancer:
| Target | IHC in bladder cancer | % positive | Internalizes |
|---|---|---|---|
| HER3 (ERBB3) | High (0.83) | 100% | yes |
| ITGAV | High (0.82) | 100% | — |
| EGFR | High (0.79) | 100% | yes |
| Nectin-4 (NECTIN4) | High (0.67) | 92% | no |
| c-MET (MET) | High (0.64) | 100% | yes |
| B7-H3 (CD276) | High (0.61) | 100% | — |
| ITGB6 | High (0.53) | 67% | — |
| STEAP2 | High (0.52) | 100% | — |
| SSTR2 | Medium (0.47) | 92% | yes |
| CEA (CEACAM5) | Medium (0.44) | 67% | — |
| FAP | Medium (0.37) | 60% | yes |
| HER2 (ERBB2) | Medium (0.33) | 58% | yes |
| TROP2 (TACSTD2) | Medium (0.30) | 55% | uncertain |
| TMEFF2 | Medium (0.28) | 75% | — |
| CAIX (CA9) | Low (0.12) | 27% | no |
| EPCAM | Low (0.07) | 11% | — |
| Mesothelin (MSLN) | Low (0.03) | 8% | yes |
| KIT | Low (0.03) | 8% | no |
Top cell-surface targets for bladder cancer radioligand therapy
A data-driven screen of every protein annotated as cell-surface. It deliberately surfaces novel, unvalidated candidates, so confirm localization and expression before prioritizing any of them.
| # | Target | IHC in bladder cancer | % positive | Internalizes | Clinical stage |
|---|---|---|---|---|---|
| 1 | EGFR epidermal growth factor receptor | High (0.79) | 100% | yes | Clinical |
| 2 | HER3 (ERBB3) erb-b2 receptor tyrosine kinase 3 | High (0.83) | 100% | yes | Clinical |
| 3 | c-MET (MET) MET proto-oncogene, receptor tyrosine kinase | High (0.64) | 100% | yes | Clinical |
| 4 | AMFR autocrine motility factor receptor | High (0.93) | 100% | yes | Discovery |
| 5 | IGF1R insulin like growth factor 1 receptor | High (0.73) | 100% | yes | Clinical |
| 6 | S1PR1 sphingosine-1-phosphate receptor 1 | High (0.58) | 82% | yes | Clinical |
| 7 | LSR lipolysis stimulated lipoprotein receptor | High (0.89) | 100% | yes | Discovery |
| 8 | FZD6 frizzled class receptor 6 | High (0.88) | 100% | yes | Discovery |
| 9 | HRH4 histamine receptor H4 | High (0.70) | 100% | yes | Clinical |
| 10 | MAOB monoamine oxidase B | High (0.94) | 100% | — | Clinical |
| 11 | NOTCH1 notch receptor 1 | High (0.64) | 100% | yes | Clinical |
| 12 | IL1R2 interleukin 1 receptor type 2 | High (0.64) | 100% | yes | Discovery |
| 13 | NR3C2 nuclear receptor subfamily 3 group C member 2 | High (0.79) | 100% | uncertain | Clinical |
| 14 | GPR139 G protein-coupled receptor 139 | High (0.82) | 100% | yes | Discovery |
| 15 | FZD3 frizzled class receptor 3 | High (0.81) | 100% | yes | Discovery |
| 16 | CHRNA7 cholinergic receptor nicotinic alpha 7 subunit | High (0.64) | 91% | yes | Clinical |
| 17 | NOTCH3 notch receptor 3 | High (0.56) | 100% | yes | Clinical |
| 18 | TNFRSF1A TNF receptor superfamily member 1A | High (0.58) | 100% | yes | Clinical |
| 19 | TREM1 triggering receptor expressed on myeloid cells 1 | High (0.72) | 92% | uncertain | Clinical |
| 20 | RNF43 ring finger protein 43 | High (0.94) | 100% | — | Discovery |
| 21 | M6PR mannose-6-phosphate receptor, cation dependent | High (0.72) | 100% | yes | Discovery |
| 22 | MST1R macrophage stimulating 1 receptor | High (0.52) | 100% | yes | Clinical |
| 23 | ADRM1 ADRM1 26S proteasome ubiquitin receptor | High (0.85) | 100% | uncertain | Clinical |
| 24 | NOTCH2 notch receptor 2 | High (0.53) | 92% | yes | Clinical |
| 25 | CSPG4 chondroitin sulfate proteoglycan 4 | High (0.94) | 100% | — | Discovery |
Internalizing receptors in bladder cancer
Targets expressed in bladder cancer that the literature reports internalize after ligand binding. Internalization traps the radionuclide inside the tumor cell, which matters most for β-emitters like 177Lu and for α-emitters like 225Ac:
EGFR · HER3 (ERBB3) · c-MET (MET) · AMFR · IGF1R · S1PR1 · LSR · FZD6 · HRH4 · NOTCH1 · IL1R2 · GPR139
Bladder Cancer targets already in clinical development
Targets with a clinical-stage drug program (any modality) that are also expressed in bladder cancer. Clinical precedent lowers development risk but usually means more competition:
EGFR · HER3 (ERBB3) · c-MET (MET) · IGF1R · S1PR1 · HRH4 · MAOB · NOTCH1 · NR3C2 · CHRNA7 · NOTCH3 · TNFRSF1A
How these bladder cancer targets are ranked
Candidates are limited to proteins annotated as cell-surface (UniProt via Open Targets), because a radioligand has to reach its target from circulation. They are ranked by Nuclens' radiopharmaceutical pre-screen: immunohistochemistry staining and patient-sample positivity in bladder cancer, literature evidence of internalization and shedding, clinical maturity, and cancer association. It is a first-pass triage, not a substitute for wet-lab validation or dosimetry. For the full framework, see what makes a good radioligand therapy target and emerging radioligand targets beyond PSMA.
Rank bladder cancer targets against your own criteria: isotope, organ limits, novelty.
Run a free bladder cancer analysisRadioligand therapy targets in other cancers
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- Lymphoma
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- Skin Cancer
- Testicular Cancer
Data sources
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.