Radioligand Therapy Targets in Prostate Cancer
We screened every cell-surface protein with tumor immunohistochemistry data in prostate cancer (including metastatic castration-resistant prostate cancer (mCRPC)). 4,031 show detectable protein staining. Established and emerging radioligand targets expressed in prostate cancer include PSMA (FOLH1), EPCAM, B7-H3 (CD276) and HER3 (ERBB3). Below, we rank every candidate by tumor expression, internalization and clinical maturity.
Established and emerging radioligand targets in prostate cancer
Targets already pursued with radioligands or other targeted modalities that show protein expression in prostate cancer:
| Target | IHC in prostate cancer | % positive | Internalizes |
|---|---|---|---|
| PSMA (FOLH1) | High (1.00) | 100% | yes |
| EPCAM | High (0.94) | 100% | — |
| B7-H3 (CD276) | High (0.75) | 100% | — |
| HER3 (ERBB3) | High (0.72) | 100% | yes |
| STEAP2 | High (0.64) | 100% | — |
| FAP | High (0.53) | 90% | yes |
| TMEFF2 | High (0.53) | 92% | — |
| c-MET (MET) | Medium (0.47) | 100% | yes |
| ITGAV | Medium (0.47) | 100% | — |
| EGFR | Medium (0.39) | 67% | yes |
| Nectin-4 (NECTIN4) | Low (0.15) | 46% | no |
| CD38 | Low (0.11) | 17% | — |
| SSTR2 | Low (0.08) | 17% | yes |
| DLK1 | Low (0.06) | 18% | — |
| CD19 | Low (0.06) | 9% | — |
| STEAP1 | Low (0.04) | 11% | — |
| CD45 (PTPRC) | Low (0.03) | 8% | no |
Top cell-surface targets for prostate 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 prostate cancer | % positive | Internalizes | Clinical stage |
|---|---|---|---|---|---|
| 1 | PTPRB protein tyrosine phosphatase receptor type B | High (0.97) | 100% | yes | Clinical |
| 2 | PSMA (FOLH1) folate hydrolase 1 | High (1.00) | 100% | yes | Clinical |
| 3 | CYSLTR2 cysteinyl leukotriene receptor 2 | High (1.00) | 100% | yes | Discovery |
| 4 | AMFR autocrine motility factor receptor | High (1.00) | 100% | yes | Discovery |
| 5 | ADGRL1 adhesion G protein-coupled receptor L1 | High (1.00) | 100% | yes | Discovery |
| 6 | AGTRAP angiotensin II receptor associated protein | High (0.97) | 100% | yes | Discovery |
| 7 | IGF1R insulin like growth factor 1 receptor | High (0.73) | 100% | yes | Clinical |
| 8 | HER3 (ERBB3) erb-b2 receptor tyrosine kinase 3 | High (0.72) | 100% | yes | Clinical |
| 9 | MAOB monoamine oxidase B | High (1.00) | 100% | — | Clinical |
| 10 | FLT4 fms related receptor tyrosine kinase 4 | High (0.56) | 92% | yes | Clinical |
| 11 | GPR139 G protein-coupled receptor 139 | High (0.89) | 100% | yes | Discovery |
| 12 | NOTCH1 notch receptor 1 | High (0.67) | 100% | yes | Clinical |
| 13 | CHRM2 cholinergic receptor muscarinic 2 | High (0.92) | 100% | uncertain | Clinical |
| 14 | NR3C2 nuclear receptor subfamily 3 group C member 2 | High (0.82) | 100% | uncertain | Clinical |
| 15 | M6PR mannose-6-phosphate receptor, cation dependent | High (0.81) | 100% | yes | Discovery |
| 16 | BDKRB1 bradykinin receptor B1 | High (0.97) | 100% | uncertain | Clinical |
| 17 | FAAH fatty acid amide hydrolase | High (0.88) | 100% | — | Clinical |
| 18 | GABRP gamma-aminobutyric acid type A receptor subunit pi | High (0.94) | 100% | uncertain | Clinical |
| 19 | c-MET (MET) MET proto-oncogene, receptor tyrosine kinase | Medium (0.47) | 100% | yes | Clinical |
| 20 | ACP3 acid phosphatase 3 | High (1.00) | 100% | — | Discovery |
| 21 | IL1R2 interleukin 1 receptor type 2 | High (0.61) | 92% | yes | Discovery |
| 22 | FZD3 frizzled class receptor 3 | High (0.75) | 100% | yes | Discovery |
| 23 | NOTCH2 notch receptor 2 | High (0.56) | 100% | yes | Clinical |
| 24 | SORD sorbitol dehydrogenase | High (1.00) | 100% | — | Discovery |
| 25 | LPAR2 lysophosphatidic acid receptor 2 | High (0.75) | 100% | yes | Discovery |
Internalizing receptors in prostate cancer
Targets expressed in prostate 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:
PTPRB · PSMA (FOLH1) · CYSLTR2 · AMFR · ADGRL1 · AGTRAP · IGF1R · HER3 (ERBB3) · FLT4 · GPR139 · NOTCH1 · M6PR
Prostate Cancer targets already in clinical development
Targets with a clinical-stage drug program (any modality) that are also expressed in prostate cancer. Clinical precedent lowers development risk but usually means more competition:
PTPRB · PSMA (FOLH1) · IGF1R · HER3 (ERBB3) · MAOB · FLT4 · NOTCH1 · CHRM2 · NR3C2 · BDKRB1 · FAAH · GABRP
How these prostate 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 prostate 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 prostate cancer targets against your own criteria: isotope, organ limits, novelty.
Run a free prostate cancer analysisRadioligand therapy targets in other cancers
- Neuroendocrine Tumors
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- Colorectal Cancer
- Kidney Cancer
- Bladder Cancer
- Gastric Cancer
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- Glioma
- Melanoma
- Head and Neck Cancer
- Thyroid Cancer
- Lymphoma
- Cervical Cancer
- Endometrial Cancer
- 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.