Radioligand Therapy Targets in Colorectal Cancer
We screened every cell-surface protein with tumor immunohistochemistry data in colorectal cancer (including colon and rectal adenocarcinoma). 4,339 show detectable protein staining. Established and emerging radioligand targets expressed in colorectal cancer include EPCAM, HER3 (ERBB3), CEA (CEACAM5) and c-MET (MET). Below, we rank every candidate by tumor expression, internalization and clinical maturity.
Established and emerging radioligand targets in colorectal cancer
Targets already pursued with radioligands or other targeted modalities that show protein expression in colorectal cancer:
| Target | IHC in colorectal cancer | % positive | Internalizes |
|---|---|---|---|
| EPCAM | High (1.00) | 100% | — |
| HER3 (ERBB3) | High (0.87) | 100% | yes |
| CEA (CEACAM5) | High (0.87) | 100% | — |
| c-MET (MET) | High (0.86) | 100% | yes |
| STEAP2 | High (0.83) | 100% | — |
| FAP | High (0.80) | 100% | yes |
| SSTR2 | Medium (0.47) | 92% | yes |
| EGFR | Medium (0.44) | 83% | yes |
| B7-H3 (CD276) | Medium (0.39) | 83% | — |
| ITGAV | Medium (0.36) | 100% | — |
| TMEFF2 | Medium (0.31) | 67% | — |
| Nectin-4 (NECTIN4) | Medium (0.30) | 80% | no |
| HER2 (ERBB2) | Medium (0.24) | 46% | yes |
| Mesothelin (MSLN) | Medium (0.21) | 27% | yes |
| ITGB6 | Low (0.17) | 50% | — |
| Claudin 18.2 (CLDN18) | Low (0.11) | 17% | uncertain |
| TROP2 (TACSTD2) | Low (0.08) | 25% | uncertain |
Top cell-surface targets for colorectal 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 colorectal cancer | % positive | Internalizes | Clinical stage |
|---|---|---|---|---|---|
| 1 | NOTCH1 notch receptor 1 | High (1.00) | 100% | yes | Clinical |
| 2 | c-MET (MET) MET proto-oncogene, receptor tyrosine kinase | High (0.86) | 100% | yes | Clinical |
| 3 | CYSLTR2 cysteinyl leukotriene receptor 2 | High (0.92) | 100% | yes | Discovery |
| 4 | IGF1R insulin like growth factor 1 receptor | High (0.90) | 100% | yes | Clinical |
| 5 | HER3 (ERBB3) erb-b2 receptor tyrosine kinase 3 | High (0.87) | 100% | yes | Clinical |
| 6 | NR3C2 nuclear receptor subfamily 3 group C member 2 | High (0.97) | 100% | uncertain | Clinical |
| 7 | FZD3 frizzled class receptor 3 | High (0.97) | 100% | yes | Discovery |
| 8 | IRAK4 interleukin 1 receptor associated kinase 4 | High (0.82) | 100% | yes | Clinical |
| 9 | ADGRL1 adhesion G protein-coupled receptor L1 | High (0.94) | 100% | yes | Discovery |
| 10 | FZD6 frizzled class receptor 6 | High (0.92) | 100% | yes | Discovery |
| 11 | GPR4 G protein-coupled receptor 4 | High (0.77) | 90% | yes | Discovery |
| 12 | AMFR autocrine motility factor receptor | High (0.92) | 92% | yes | Discovery |
| 13 | NOTCH3 notch receptor 3 | High (0.69) | 100% | yes | Clinical |
| 14 | HRH4 histamine receptor H4 | High (0.72) | 100% | yes | Clinical |
| 15 | CHRNA7 cholinergic receptor nicotinic alpha 7 subunit | High (0.70) | 100% | yes | Clinical |
| 16 | FAP fibroblast activation protein alpha | High (0.80) | 100% | yes | Clinical |
| 17 | M6PR mannose-6-phosphate receptor, cation dependent | High (0.86) | 100% | yes | Discovery |
| 18 | IL1R2 interleukin 1 receptor type 2 | High (0.67) | 100% | yes | Discovery |
| 19 | PTPN22 protein tyrosine phosphatase non-receptor type 22 | High (0.83) | 100% | yes | Discovery |
| 20 | S1PR1 sphingosine-1-phosphate receptor 1 | Medium (0.47) | 100% | yes | Clinical |
| 21 | GABRE gamma-aminobutyric acid type A receptor subunit epsilon | High (1.00) | 100% | uncertain | Clinical |
| 22 | GPER1 G protein-coupled estrogen receptor 1 | High (0.83) | 100% | yes | Discovery |
| 23 | PTPN13 protein tyrosine phosphatase non-receptor type 13 | High (0.81) | 100% | yes | Discovery |
| 24 | EPHB4 EPH receptor B4 | High (0.67) | 92% | yes | Clinical |
| 25 | LSR lipolysis stimulated lipoprotein receptor | High (0.83) | 100% | yes | Discovery |
Internalizing receptors in colorectal cancer
Targets expressed in colorectal 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:
NOTCH1 · c-MET (MET) · CYSLTR2 · IGF1R · HER3 (ERBB3) · FZD3 · IRAK4 · ADGRL1 · FZD6 · GPR4 · AMFR · NOTCH3
Colorectal Cancer targets already in clinical development
Targets with a clinical-stage drug program (any modality) that are also expressed in colorectal cancer. Clinical precedent lowers development risk but usually means more competition:
NOTCH1 · c-MET (MET) · IGF1R · HER3 (ERBB3) · NR3C2 · IRAK4 · NOTCH3 · HRH4 · CHRNA7 · FAP · S1PR1 · GABRE
How these colorectal 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 colorectal 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 colorectal cancer targets against your own criteria: isotope, organ limits, novelty.
Run a free colorectal cancer analysisRadioligand therapy targets in other cancers
- Prostate Cancer
- Neuroendocrine Tumors
- Lung Cancer
- Pancreatic Cancer
- Breast Cancer
- Ovarian Cancer
- Kidney Cancer
- Bladder Cancer
- Gastric Cancer
- Liver Cancer
- 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.