Radioligand Therapy Targets in Liver Cancer
We screened every cell-surface protein with tumor immunohistochemistry data in liver cancer (including hepatocellular carcinoma (HCC)). 4,436 show detectable protein staining. Established and emerging radioligand targets expressed in liver cancer include EGFR, STEAP2, HER3 (ERBB3) and c-MET (MET). Below, we rank every candidate by tumor expression, internalization and clinical maturity.
Established and emerging radioligand targets in liver cancer
Targets already pursued with radioligands or other targeted modalities that show protein expression in liver cancer:
| Target | IHC in liver cancer | % positive | Internalizes |
|---|---|---|---|
| EGFR | High (0.88) | 100% | yes |
| STEAP2 | High (0.83) | 100% | — |
| HER3 (ERBB3) | High (0.70) | 91% | yes |
| c-MET (MET) | High (0.60) | 100% | yes |
| SSTR2 | High (0.56) | 92% | yes |
| B7-H3 (CD276) | Medium (0.44) | 83% | — |
| TMEFF2 | Medium (0.39) | 67% | — |
| ITGAV | Medium (0.36) | 67% | — |
| Nectin-4 (NECTIN4) | Medium (0.27) | 70% | no |
| Claudin 18.2 (CLDN18) | Medium (0.22) | 22% | uncertain |
| Mesothelin (MSLN) | Medium (0.20) | 30% | yes |
| HER2 (ERBB2) | Low (0.19) | 58% | yes |
| CEA (CEACAM5) | Low (0.19) | 29% | — |
| FAP | Low (0.15) | 27% | yes |
| TROP2 (TACSTD2) | Low (0.06) | 9% | uncertain |
| CAIX (CA9) | Low (0.06) | 9% | no |
| CD19 | Low (0.03) | 10% | — |
| CD38 | Low (0.03) | 9% | — |
| ITGB6 | Low (0.03) | 8% | — |
Top cell-surface targets for liver 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 liver cancer | % positive | Internalizes | Clinical stage |
|---|---|---|---|---|---|
| 1 | EGFR epidermal growth factor receptor | High (0.88) | 100% | yes | Clinical |
| 2 | IGF1R insulin like growth factor 1 receptor | High (0.85) | 100% | yes | Clinical |
| 3 | AMFR autocrine motility factor receptor | High (1.00) | 100% | yes | Discovery |
| 4 | GPR139 G protein-coupled receptor 139 | High (1.00) | 100% | yes | Discovery |
| 5 | IL1R2 interleukin 1 receptor type 2 | High (0.81) | 100% | yes | Discovery |
| 6 | LIFR LIF receptor subunit alpha | High (0.97) | 100% | yes | Discovery |
| 7 | S1PR1 sphingosine-1-phosphate receptor 1 | High (0.61) | 100% | yes | Clinical |
| 8 | CYSLTR2 cysteinyl leukotriene receptor 2 | High (0.81) | 100% | yes | Discovery |
| 9 | NR3C2 nuclear receptor subfamily 3 group C member 2 | High (0.89) | 100% | uncertain | Clinical |
| 10 | CCRL2 C-C motif chemokine receptor like 2 | High (0.75) | 100% | yes | Discovery |
| 11 | c-MET (MET) MET proto-oncogene, receptor tyrosine kinase | High (0.60) | 100% | yes | Clinical |
| 12 | NOTCH1 notch receptor 1 | High (0.67) | 100% | yes | Clinical |
| 13 | HER3 (ERBB3) erb-b2 receptor tyrosine kinase 3 | High (0.70) | 91% | yes | Clinical |
| 14 | MST1R macrophage stimulating 1 receptor | High (0.67) | 100% | yes | Clinical |
| 15 | FZD6 frizzled class receptor 6 | High (0.86) | 100% | yes | Discovery |
| 16 | CHRM2 cholinergic receptor muscarinic 2 | High (0.89) | 100% | uncertain | Clinical |
| 17 | FZD3 frizzled class receptor 3 | High (0.81) | 100% | yes | Discovery |
| 18 | FLT4 fms related receptor tyrosine kinase 4 | Medium (0.47) | 92% | yes | Clinical |
| 19 | M6PR mannose-6-phosphate receptor, cation dependent | High (0.81) | 100% | yes | Discovery |
| 20 | MAOB monoamine oxidase B | High (0.89) | 100% | — | Clinical |
| 21 | IRAK4 interleukin 1 receptor associated kinase 4 | High (0.64) | 100% | yes | Clinical |
| 22 | CHRNA7 cholinergic receptor nicotinic alpha 7 subunit | High (0.61) | 100% | yes | Clinical |
| 23 | TREM1 triggering receptor expressed on myeloid cells 1 | High (0.74) | 100% | uncertain | Clinical |
| 24 | HMGA1 high mobility group AT-hook 1 | High (0.97) | 100% | — | Discovery |
| 25 | SSTR2 somatostatin receptor 2 | High (0.56) | 92% | yes | Clinical |
Internalizing receptors in liver cancer
Targets expressed in liver 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 · IGF1R · AMFR · GPR139 · IL1R2 · LIFR · S1PR1 · CYSLTR2 · CCRL2 · c-MET (MET) · NOTCH1 · HER3 (ERBB3)
Liver Cancer targets already in clinical development
Targets with a clinical-stage drug program (any modality) that are also expressed in liver cancer. Clinical precedent lowers development risk but usually means more competition:
EGFR · IGF1R · S1PR1 · NR3C2 · c-MET (MET) · NOTCH1 · HER3 (ERBB3) · MST1R · CHRM2 · FLT4 · MAOB · IRAK4
How these liver 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 liver 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 liver cancer targets against your own criteria: isotope, organ limits, novelty.
Run a free liver cancer analysisRadioligand therapy targets in other cancers
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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.