Radioligand Therapy Targets in Pancreatic Cancer
We screened every cell-surface protein with tumor immunohistochemistry data in pancreatic cancer (including pancreatic ductal adenocarcinoma (PDAC)). 4,357 show detectable protein staining. Established and emerging radioligand targets expressed in pancreatic cancer include HER3 (ERBB3), FAP, STEAP2 and c-MET (MET). Below, we rank every candidate by tumor expression, internalization and clinical maturity.
Established and emerging radioligand targets in pancreatic cancer
Targets already pursued with radioligands or other targeted modalities that show protein expression in pancreatic cancer:
| Target | IHC in pancreatic cancer | % positive | Internalizes |
|---|---|---|---|
| HER3 (ERBB3) | High (0.88) | 100% | yes |
| FAP | High (0.74) | 89% | yes |
| STEAP2 | High (0.70) | 100% | — |
| c-MET (MET) | High (0.67) | 100% | yes |
| Mesothelin (MSLN) | High (0.64) | 83% | yes |
| EGFR | High (0.64) | 100% | yes |
| CEA (CEACAM5) | High (0.64) | 91% | — |
| B7-H3 (CD276) | High (0.56) | 100% | — |
| ITGAV | High (0.56) | 89% | — |
| ITGB6 | Medium (0.37) | 70% | — |
| SSTR2 | Medium (0.31) | 58% | yes |
| Claudin 18.2 (CLDN18) | Medium (0.30) | 40% | uncertain |
| TMEFF2 | Medium (0.25) | 67% | — |
| Nectin-4 (NECTIN4) | Medium (0.22) | 42% | no |
| HER2 (ERBB2) | Low (0.18) | 46% | yes |
| TROP2 (TACSTD2) | Low (0.12) | 27% | uncertain |
| DLK1 | Low (0.06) | 8% | — |
| EPCAM | Low (0.04) | 11% | — |
| CAIX (CA9) | Low (0.03) | 10% | no |
| CD19 | Low (0.03) | 10% | — |
| PSMA (FOLH1) | Low (0.03) | 8% | yes |
| KIT | Low (0.03) | 8% | no |
Top cell-surface targets for pancreatic 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 pancreatic cancer | % positive | Internalizes | Clinical stage |
|---|---|---|---|---|---|
| 1 | CYSLTR2 cysteinyl leukotriene receptor 2 | High (0.94) | 100% | yes | Discovery |
| 2 | EGFR epidermal growth factor receptor | High (0.64) | 100% | yes | Clinical |
| 3 | HER3 (ERBB3) erb-b2 receptor tyrosine kinase 3 | High (0.88) | 100% | yes | Clinical |
| 4 | AMFR autocrine motility factor receptor | High (1.00) | 100% | yes | Discovery |
| 5 | IGF1R insulin like growth factor 1 receptor | High (0.82) | 100% | yes | Clinical |
| 6 | c-MET (MET) MET proto-oncogene, receptor tyrosine kinase | High (0.67) | 100% | yes | Clinical |
| 7 | NOTCH1 notch receptor 1 | High (0.75) | 100% | yes | Clinical |
| 8 | GPR139 G protein-coupled receptor 139 | High (0.94) | 100% | yes | Discovery |
| 9 | LIFR LIF receptor subunit alpha | High (0.88) | 100% | yes | Discovery |
| 10 | Mesothelin (MSLN) mesothelin | High (0.64) | 83% | yes | Clinical |
| 11 | IRAK4 interleukin 1 receptor associated kinase 4 | High (0.70) | 100% | yes | Clinical |
| 12 | HRH4 histamine receptor H4 | High (0.70) | 100% | yes | Clinical |
| 13 | MAOB monoamine oxidase B | High (0.94) | 100% | — | Clinical |
| 14 | NR3C2 nuclear receptor subfamily 3 group C member 2 | High (0.80) | 100% | uncertain | Clinical |
| 15 | ITPR3 inositol 1,4,5-trisphosphate receptor type 3 | High (0.83) | 100% | yes | Discovery |
| 16 | VIPR1 vasoactive intestinal peptide receptor 1 | High (0.61) | 100% | yes | Discovery |
| 17 | IL1R2 interleukin 1 receptor type 2 | High (0.61) | 92% | yes | Discovery |
| 18 | FZD6 frizzled class receptor 6 | High (0.77) | 100% | yes | Discovery |
| 19 | FAP fibroblast activation protein alpha | High (0.74) | 89% | yes | Clinical |
| 20 | CHRNA7 cholinergic receptor nicotinic alpha 7 subunit | High (0.58) | 100% | yes | Clinical |
| 21 | AGTRAP angiotensin II receptor associated protein | High (0.75) | 92% | yes | Discovery |
| 22 | S1PR1 sphingosine-1-phosphate receptor 1 | Medium (0.42) | 83% | yes | Clinical |
| 23 | FZD3 frizzled class receptor 3 | High (0.76) | 91% | yes | Discovery |
| 24 | FGFR1 fibroblast growth factor receptor 1 | High (0.52) | 100% | yes | Clinical |
| 25 | IL18R1 interleukin 18 receptor 1 | High (0.89) | 100% | uncertain | Clinical |
Internalizing receptors in pancreatic cancer
Targets expressed in pancreatic 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:
CYSLTR2 · EGFR · HER3 (ERBB3) · AMFR · IGF1R · c-MET (MET) · NOTCH1 · GPR139 · LIFR · Mesothelin (MSLN) · IRAK4 · HRH4
Pancreatic Cancer targets already in clinical development
Targets with a clinical-stage drug program (any modality) that are also expressed in pancreatic cancer. Clinical precedent lowers development risk but usually means more competition:
EGFR · HER3 (ERBB3) · IGF1R · c-MET (MET) · NOTCH1 · Mesothelin (MSLN) · IRAK4 · HRH4 · MAOB · NR3C2 · FAP · CHRNA7
How these pancreatic 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 pancreatic 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 pancreatic cancer targets against your own criteria: isotope, organ limits, novelty.
Run a free pancreatic cancer analysisRadioligand therapy targets in other cancers
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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.