Radioligand Therapy Targets in Breast Cancer
We screened every cell-surface protein with tumor immunohistochemistry data in breast cancer (including triple-negative (TNBC) and HER2-positive subtypes). 4,328 show detectable protein staining. Established and emerging radioligand targets expressed in breast cancer include HER3 (ERBB3), FAP, STEAP2 and B7-H3 (CD276). Below, we rank every candidate by tumor expression, internalization and clinical maturity.
Established and emerging radioligand targets in breast cancer
Targets already pursued with radioligands or other targeted modalities that show protein expression in breast cancer:
| Target | IHC in breast cancer | % positive | Internalizes |
|---|---|---|---|
| HER3 (ERBB3) | High (0.91) | 100% | yes |
| FAP | High (0.77) | 90% | yes |
| STEAP2 | High (0.70) | 100% | — |
| B7-H3 (CD276) | High (0.58) | 100% | — |
| c-MET (MET) | High (0.58) | 100% | yes |
| HER2 (ERBB2) | High (0.52) | 64% | yes |
| ITGAV | Medium (0.50) | 83% | — |
| TMEFF2 | Medium (0.44) | 83% | — |
| EPCAM | Medium (0.36) | 50% | — |
| Nectin-4 (NECTIN4) | Medium (0.28) | 75% | no |
| ITGB6 | Low (0.19) | 25% | — |
| SSTR2 | Low (0.18) | 55% | yes |
| EGFR | Low (0.17) | 30% | yes |
| Mesothelin (MSLN) | Low (0.14) | 17% | yes |
| CD38 | Low (0.03) | 8% | — |
| DLK1 | Low (0.03) | 8% | — |
Top cell-surface targets for breast 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 breast cancer | % positive | Internalizes | Clinical stage |
|---|---|---|---|---|---|
| 1 | HER3 (ERBB3) erb-b2 receptor tyrosine kinase 3 | High (0.91) | 100% | yes | Clinical |
| 2 | ESR1 estrogen receptor 1 | High (0.70) | 70% | yes | Clinical |
| 3 | IGF1R insulin like growth factor 1 receptor | High (0.82) | 100% | yes | Clinical |
| 4 | CYSLTR2 cysteinyl leukotriene receptor 2 | High (0.83) | 92% | yes | Discovery |
| 5 | AMFR autocrine motility factor receptor | High (0.93) | 100% | yes | Discovery |
| 6 | NR3C2 nuclear receptor subfamily 3 group C member 2 | High (0.86) | 100% | uncertain | Clinical |
| 7 | GPR139 G protein-coupled receptor 139 | High (0.89) | 100% | yes | Discovery |
| 8 | c-MET (MET) MET proto-oncogene, receptor tyrosine kinase | High (0.58) | 100% | yes | Clinical |
| 9 | FGFR1 fibroblast growth factor receptor 1 | High (0.67) | 100% | yes | Clinical |
| 10 | S1PR1 sphingosine-1-phosphate receptor 1 | High (0.56) | 83% | yes | Clinical |
| 11 | IL1R2 interleukin 1 receptor type 2 | High (0.67) | 100% | yes | Discovery |
| 12 | IRAK4 interleukin 1 receptor associated kinase 4 | High (0.69) | 100% | yes | Clinical |
| 13 | CHRM2 cholinergic receptor muscarinic 2 | High (0.91) | 100% | uncertain | Clinical |
| 14 | NOTCH1 notch receptor 1 | High (0.64) | 100% | yes | Clinical |
| 15 | MST1R macrophage stimulating 1 receptor | High (0.64) | 100% | yes | Clinical |
| 16 | HRH4 histamine receptor H4 | High (0.67) | 100% | yes | Clinical |
| 17 | MAOB monoamine oxidase B | High (0.92) | 100% | — | Clinical |
| 18 | VIPR1 vasoactive intestinal peptide receptor 1 | High (0.61) | 100% | yes | Discovery |
| 19 | FAP fibroblast activation protein alpha | High (0.77) | 90% | yes | Clinical |
| 20 | SCTR secretin receptor | High (0.92) | 100% | uncertain | Discovery |
| 21 | LSR lipolysis stimulated lipoprotein receptor | High (0.79) | 100% | yes | Discovery |
| 22 | BDKRB1 bradykinin receptor B1 | High (0.94) | 100% | uncertain | Clinical |
| 23 | TAAR1 trace amine associated receptor 1 | High (0.85) | 100% | uncertain | Clinical |
| 24 | HTR2B 5-hydroxytryptamine receptor 2B | High (0.83) | 92% | uncertain | Clinical |
| 25 | FAAH fatty acid amide hydrolase | High (0.85) | 100% | — | Clinical |
Internalizing receptors in breast cancer
Targets expressed in breast 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) · ESR1 · IGF1R · CYSLTR2 · AMFR · GPR139 · c-MET (MET) · FGFR1 · S1PR1 · IL1R2 · IRAK4 · NOTCH1
Breast Cancer targets already in clinical development
Targets with a clinical-stage drug program (any modality) that are also expressed in breast cancer. Clinical precedent lowers development risk but usually means more competition:
HER3 (ERBB3) · ESR1 · IGF1R · NR3C2 · c-MET (MET) · FGFR1 · S1PR1 · IRAK4 · CHRM2 · NOTCH1 · MST1R · HRH4
How these breast 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 breast 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 breast cancer targets against your own criteria: isotope, organ limits, novelty.
Run a free breast cancer analysisRadioligand therapy targets in other cancers
- Prostate Cancer
- Neuroendocrine Tumors
- Lung Cancer
- Pancreatic Cancer
- Ovarian Cancer
- Colorectal 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.