Radioligand Therapy Targets in Skin Cancer
We screened every cell-surface protein with tumor immunohistochemistry data in skin cancer (including non-melanoma skin cancers). 3,878 show detectable protein staining. Established and emerging radioligand targets expressed in skin cancer include B7-H3 (CD276), EGFR, HER3 (ERBB3) and c-MET (MET). Below, we rank every candidate by tumor expression, internalization and clinical maturity.
Established and emerging radioligand targets in skin cancer
Targets already pursued with radioligands or other targeted modalities that show protein expression in skin cancer:
| Target | IHC in skin cancer | % positive | Internalizes |
|---|---|---|---|
| B7-H3 (CD276) | High (0.83) | 100% | — |
| EGFR | High (0.75) | 100% | yes |
| HER3 (ERBB3) | High (0.60) | 100% | yes |
| c-MET (MET) | High (0.58) | 100% | yes |
| ITGAV | Medium (0.48) | 64% | — |
| ITGB6 | Medium (0.47) | 83% | — |
| SSTR2 | Medium (0.42) | 67% | yes |
| TROP2 (TACSTD2) | Medium (0.39) | 73% | uncertain |
| Nectin-4 (NECTIN4) | Medium (0.33) | 67% | no |
| EPCAM | Medium (0.31) | 33% | — |
| STEAP2 | Medium (0.28) | 58% | — |
| TMEFF2 | Medium (0.27) | 55% | — |
| FAP | Low (0.14) | 25% | yes |
| HER2 (ERBB2) | Low (0.11) | 33% | yes |
| CEA (CEACAM5) | Low (0.09) | 27% | — |
| DLK1 | Low (0.07) | 10% | — |
| Mesothelin (MSLN) | Low (0.03) | 8% | yes |
Top cell-surface targets for skin 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 skin cancer | % positive | Internalizes | Clinical stage |
|---|---|---|---|---|---|
| 1 | EGFR epidermal growth factor receptor | High (0.75) | 100% | yes | Clinical |
| 2 | CALCRL calcitonin receptor like receptor | High (0.94) | 100% | uncertain | Clinical |
| 3 | S1PR1 sphingosine-1-phosphate receptor 1 | High (0.58) | 100% | yes | Clinical |
| 4 | FZD6 frizzled class receptor 6 | High (0.94) | 100% | yes | Discovery |
| 5 | GPR139 G protein-coupled receptor 139 | High (0.93) | 100% | yes | Discovery |
| 6 | AMFR autocrine motility factor receptor | High (0.91) | 100% | yes | Discovery |
| 7 | c-MET (MET) MET proto-oncogene, receptor tyrosine kinase | High (0.58) | 100% | yes | Clinical |
| 8 | HER3 (ERBB3) erb-b2 receptor tyrosine kinase 3 | High (0.60) | 100% | yes | Clinical |
| 9 | HRH4 histamine receptor H4 | High (0.64) | 100% | yes | Clinical |
| 10 | NOTCH2 notch receptor 2 | High (0.55) | 100% | yes | Clinical |
| 11 | VIPR2 vasoactive intestinal peptide receptor 2 | High (0.61) | 92% | yes | Discovery |
| 12 | SCTR secretin receptor | High (0.85) | 100% | uncertain | Discovery |
| 13 | GABRP gamma-aminobutyric acid type A receptor subunit pi | High (0.86) | 100% | uncertain | Clinical |
| 14 | BCL2L2-PABPN1 BCL2L2-PABPN1 readthrough | High (1.00) | 100% | — | Clinical |
| 15 | CTNNB1 catenin beta 1 | High (0.97) | 100% | — | Clinical |
| 16 | RNF43 ring finger protein 43 | High (0.92) | 100% | — | Discovery |
| 17 | EPHA10 EPH receptor A10 | High (0.69) | 92% | yes | Discovery |
| 18 | FGFR2 fibroblast growth factor receptor 2 | High (0.81) | 100% | uncertain | Clinical |
| 19 | FZD3 frizzled class receptor 3 | High (0.67) | 100% | yes | Discovery |
| 20 | NR3C2 nuclear receptor subfamily 3 group C member 2 | High (0.64) | 100% | uncertain | Clinical |
| 21 | NOTCH1 notch receptor 1 | High (0.53) | 83% | yes | Clinical |
| 22 | PLD4 phospholipase D family member 4 | High (0.97) | 100% | — | Discovery |
| 23 | MST1R macrophage stimulating 1 receptor | Medium (0.50) | 92% | yes | Clinical |
| 24 | IL1R2 interleukin 1 receptor type 2 | Medium (0.47) | 100% | yes | Discovery |
| 25 | NOTCH3 notch receptor 3 | High (0.53) | 83% | yes | Clinical |
Internalizing receptors in skin cancer
Targets expressed in skin 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 · S1PR1 · FZD6 · GPR139 · AMFR · c-MET (MET) · HER3 (ERBB3) · HRH4 · NOTCH2 · VIPR2 · EPHA10 · FZD3
Skin Cancer targets already in clinical development
Targets with a clinical-stage drug program (any modality) that are also expressed in skin cancer. Clinical precedent lowers development risk but usually means more competition:
EGFR · CALCRL · S1PR1 · c-MET (MET) · HER3 (ERBB3) · HRH4 · NOTCH2 · GABRP · BCL2L2-PABPN1 · CTNNB1 · FGFR2 · NR3C2
How these skin 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 skin 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 skin cancer targets against your own criteria: isotope, organ limits, novelty.
Run a free skin cancer analysisRadioligand therapy targets in other cancers
- Prostate Cancer
- Neuroendocrine Tumors
- Lung Cancer
- Pancreatic Cancer
- Breast 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
- 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.