Radioligand Therapy Targets in Head and Neck Cancer
We screened every cell-surface protein with tumor immunohistochemistry data in head and neck cancer (including head and neck squamous cell carcinoma (HNSCC)). 3,879 show detectable protein staining. Established and emerging radioligand targets expressed in head and neck cancer include EGFR, ITGAV, HER3 (ERBB3) and B7-H3 (CD276). Below, we rank every candidate by tumor expression, internalization and clinical maturity.
Established and emerging radioligand targets in head and neck cancer
Targets already pursued with radioligands or other targeted modalities that show protein expression in head and neck cancer:
| Target | IHC in head and neck cancer | % positive | Internalizes |
|---|---|---|---|
| EGFR | High (1.00) | 100% | yes |
| ITGAV | High (0.83) | 100% | — |
| HER3 (ERBB3) | High (0.75) | 100% | yes |
| B7-H3 (CD276) | High (0.75) | 100% | — |
| c-MET (MET) | High (0.75) | 100% | yes |
| STEAP2 | High (0.67) | 100% | — |
| SSTR2 | Medium (0.42) | 75% | yes |
| CEA (CEACAM5) | Medium (0.42) | 75% | — |
| EPCAM | Medium (0.42) | 50% | — |
| TMEFF2 | Medium (0.42) | 100% | — |
| ITGB6 | Medium (0.33) | 75% | — |
| HER2 (ERBB2) | Medium (0.25) | 25% | yes |
| TROP2 (TACSTD2) | Low (0.17) | 50% | uncertain |
| Mesothelin (MSLN) | Low (0.17) | 50% | yes |
| FAP | Low (0.17) | 50% | yes |
| Nectin-4 (NECTIN4) | Low (0.08) | 25% | no |
Top cell-surface targets for head and neck 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 head and neck cancer | % positive | Internalizes | Clinical stage |
|---|---|---|---|---|---|
| 1 | EGFR epidermal growth factor receptor | High (1.00) | 100% | yes | Clinical |
| 2 | c-MET (MET) MET proto-oncogene, receptor tyrosine kinase | High (0.75) | 100% | yes | Clinical |
| 3 | FGFR1 fibroblast growth factor receptor 1 | High (0.83) | 100% | yes | Clinical |
| 4 | S1PR1 sphingosine-1-phosphate receptor 1 | High (0.67) | 100% | yes | Clinical |
| 5 | VIPR2 vasoactive intestinal peptide receptor 2 | High (0.89) | 100% | yes | Discovery |
| 6 | AMFR autocrine motility factor receptor | High (1.00) | 100% | yes | Discovery |
| 7 | GPR139 G protein-coupled receptor 139 | High (1.00) | 100% | yes | Discovery |
| 8 | HER3 (ERBB3) erb-b2 receptor tyrosine kinase 3 | High (0.75) | 100% | yes | Clinical |
| 9 | NOTCH1 notch receptor 1 | High (0.75) | 100% | yes | Clinical |
| 10 | IGF1R insulin like growth factor 1 receptor | High (0.75) | 100% | yes | Clinical |
| 11 | FZD6 frizzled class receptor 6 | High (0.92) | 100% | yes | Discovery |
| 12 | HRH4 histamine receptor H4 | High (0.75) | 100% | yes | Clinical |
| 13 | TREM1 triggering receptor expressed on myeloid cells 1 | High (0.83) | 100% | uncertain | Clinical |
| 14 | IL1R2 interleukin 1 receptor type 2 | High (0.67) | 100% | yes | Discovery |
| 15 | TFRC transferrin receptor | High (1.00) | 100% | uncertain | Clinical |
| 16 | FZD3 frizzled class receptor 3 | High (0.83) | 100% | yes | Discovery |
| 17 | CHRNA7 cholinergic receptor nicotinic alpha 7 subunit | High (0.67) | 100% | yes | Clinical |
| 18 | BDKRB1 bradykinin receptor B1 | High (1.00) | 100% | uncertain | Clinical |
| 19 | NR3C2 nuclear receptor subfamily 3 group C member 2 | High (0.78) | 100% | uncertain | Clinical |
| 20 | ADRM1 ADRM1 26S proteasome ubiquitin receptor | High (0.92) | 100% | uncertain | Clinical |
| 21 | VIPR1 vasoactive intestinal peptide receptor 1 | High (0.58) | 100% | yes | Discovery |
| 22 | FAAH fatty acid amide hydrolase | High (0.83) | 100% | — | Clinical |
| 23 | ITPR3 inositol 1,4,5-trisphosphate receptor type 3 | High (0.75) | 100% | yes | Discovery |
| 24 | LSR lipolysis stimulated lipoprotein receptor | High (0.75) | 100% | yes | Discovery |
| 25 | SLC22A3 solute carrier family 22 member 3 | High (1.00) | 100% | — | Discovery |
Internalizing receptors in head and neck cancer
Targets expressed in head and neck 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 · c-MET (MET) · FGFR1 · S1PR1 · VIPR2 · AMFR · GPR139 · HER3 (ERBB3) · NOTCH1 · IGF1R · FZD6 · HRH4
Head and Neck Cancer targets already in clinical development
Targets with a clinical-stage drug program (any modality) that are also expressed in head and neck cancer. Clinical precedent lowers development risk but usually means more competition:
EGFR · c-MET (MET) · FGFR1 · S1PR1 · HER3 (ERBB3) · NOTCH1 · IGF1R · HRH4 · TREM1 · TFRC · CHRNA7 · BDKRB1
How these head and neck 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 head and neck 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 head and neck cancer targets against your own criteria: isotope, organ limits, novelty.
Run a free head and neck cancer analysisRadioligand therapy targets in other cancers
- Prostate Cancer
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- Kidney Cancer
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- Gastric Cancer
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- Glioma
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- 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.