Radioligand Therapy Targets in Gastric Cancer
We screened every cell-surface protein with tumor immunohistochemistry data in gastric cancer (including stomach adenocarcinoma). 4,158 show detectable protein staining. Established and emerging radioligand targets expressed in gastric cancer include HER3 (ERBB3), CEA (CEACAM5), FAP and c-MET (MET). Below, we rank every candidate by tumor expression, internalization and clinical maturity.
Established and emerging radioligand targets in gastric cancer
Targets already pursued with radioligands or other targeted modalities that show protein expression in gastric cancer:
| Target | IHC in gastric cancer | % positive | Internalizes |
|---|---|---|---|
| HER3 (ERBB3) | High (0.93) | 100% | yes |
| CEA (CEACAM5) | High (0.73) | 91% | — |
| FAP | High (0.70) | 100% | yes |
| c-MET (MET) | High (0.64) | 100% | yes |
| STEAP2 | High (0.64) | 100% | — |
| B7-H3 (CD276) | High (0.53) | 100% | — |
| SSTR2 | Medium (0.50) | 83% | yes |
| Claudin 18.2 (CLDN18) | Medium (0.44) | 50% | uncertain |
| ITGAV | Medium (0.39) | 67% | — |
| EGFR | Medium (0.36) | 73% | yes |
| Mesothelin (MSLN) | Medium (0.33) | 50% | yes |
| TMEFF2 | Medium (0.30) | 55% | — |
| CAIX (CA9) | Medium (0.21) | 36% | no |
| EPCAM | Low (0.17) | 30% | — |
| HER2 (ERBB2) | Low (0.11) | 17% | yes |
| ITGB6 | Low (0.10) | 20% | — |
| Nectin-4 (NECTIN4) | Low (0.07) | 20% | no |
| PSCA | Low (0.06) | 8% | — |
| STEAP1 | Low (0.03) | 10% | — |
Top cell-surface targets for gastric 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 gastric cancer | % positive | Internalizes | Clinical stage |
|---|---|---|---|---|---|
| 1 | HER3 (ERBB3) erb-b2 receptor tyrosine kinase 3 | High (0.93) | 100% | yes | Clinical |
| 2 | IGF1R insulin like growth factor 1 receptor | High (0.86) | 100% | yes | Clinical |
| 3 | CYSLTR2 cysteinyl leukotriene receptor 2 | High (0.86) | 92% | yes | Discovery |
| 4 | AMFR autocrine motility factor receptor | High (1.00) | 100% | yes | Discovery |
| 5 | LIFR LIF receptor subunit alpha | High (0.97) | 100% | yes | Discovery |
| 6 | c-MET (MET) MET proto-oncogene, receptor tyrosine kinase | High (0.64) | 100% | yes | Clinical |
| 7 | GPR139 G protein-coupled receptor 139 | High (0.94) | 100% | yes | Discovery |
| 8 | NR3C2 nuclear receptor subfamily 3 group C member 2 | High (0.83) | 100% | uncertain | Clinical |
| 9 | CHRNA7 cholinergic receptor nicotinic alpha 7 subunit | High (0.67) | 100% | yes | Clinical |
| 10 | IRAK4 interleukin 1 receptor associated kinase 4 | High (0.67) | 100% | yes | Clinical |
| 11 | MAOB monoamine oxidase B | High (0.91) | 100% | — | Clinical |
| 12 | FZD3 frizzled class receptor 3 | High (0.79) | 100% | yes | Discovery |
| 13 | ADGRL1 adhesion G protein-coupled receptor L1 | High (0.82) | 91% | yes | Discovery |
| 14 | NOTCH1 notch receptor 1 | High (0.58) | 100% | yes | Clinical |
| 15 | HRH4 histamine receptor H4 | High (0.61) | 100% | yes | Clinical |
| 16 | FAP fibroblast activation protein alpha | High (0.70) | 100% | yes | Clinical |
| 17 | IL18R1 interleukin 18 receptor 1 | High (0.91) | 100% | uncertain | Clinical |
| 18 | HMGA1 high mobility group AT-hook 1 | High (0.97) | 100% | — | Discovery |
| 19 | ITPR3 inositol 1,4,5-trisphosphate receptor type 3 | High (0.73) | 100% | yes | Discovery |
| 20 | ATAD3B ATPase family AAA domain containing 3B | High (1.00) | 100% | — | Discovery |
| 21 | GABRE gamma-aminobutyric acid type A receptor subunit epsilon | High (0.87) | 100% | uncertain | Clinical |
| 22 | SEMA6A semaphorin 6A | High (0.96) | 100% | — | Discovery |
| 23 | BCL2L2-PABPN1 BCL2L2-PABPN1 readthrough | High (1.00) | 100% | — | Clinical |
| 24 | MUC1 mucin 1, cell surface associated | High (1.00) | 100% | — | Clinical |
| 25 | EGFR epidermal growth factor receptor | Medium (0.36) | 73% | yes | Clinical |
Internalizing receptors in gastric cancer
Targets expressed in gastric 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:
HER3 (ERBB3) · IGF1R · CYSLTR2 · AMFR · LIFR · c-MET (MET) · GPR139 · CHRNA7 · IRAK4 · FZD3 · ADGRL1 · NOTCH1
Gastric Cancer targets already in clinical development
Targets with a clinical-stage drug program (any modality) that are also expressed in gastric cancer. Clinical precedent lowers development risk but usually means more competition:
HER3 (ERBB3) · IGF1R · c-MET (MET) · NR3C2 · CHRNA7 · IRAK4 · MAOB · NOTCH1 · HRH4 · FAP · IL18R1 · GABRE
How these gastric 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 gastric 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 gastric cancer targets against your own criteria: isotope, organ limits, novelty.
Run a free gastric cancer analysisRadioligand therapy targets in other cancers
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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.