Radioligand Therapy Targets in Melanoma
We screened every cell-surface protein with tumor immunohistochemistry data in melanoma (including cutaneous melanoma). 4,224 show detectable protein staining. Established and emerging radioligand targets expressed in melanoma include HER3 (ERBB3), STEAP2, B7-H3 (CD276) and c-MET (MET). Below, we rank every candidate by tumor expression, internalization and clinical maturity.
Established and emerging radioligand targets in melanoma
Targets already pursued with radioligands or other targeted modalities that show protein expression in melanoma:
| Target | IHC in melanoma | % positive | Internalizes |
|---|---|---|---|
| HER3 (ERBB3) | High (0.90) | 100% | yes |
| STEAP2 | High (0.79) | 100% | — |
| B7-H3 (CD276) | High (0.69) | 100% | — |
| c-MET (MET) | High (0.67) | 100% | yes |
| ITGAV | High (0.67) | 100% | — |
| TMEFF2 | High (0.58) | 92% | — |
| SSTR2 | Medium (0.39) | 75% | yes |
| FAP | Low (0.19) | 42% | yes |
| Nectin-4 (NECTIN4) | Low (0.08) | 25% | no |
| CD19 | Low (0.06) | 8% | — |
| HER2 (ERBB2) | Low (0.03) | 9% | yes |
| Claudin 18.2 (CLDN18) | Low (0.03) | 8% | uncertain |
| KIT | Low (0.03) | 8% | no |
Top cell-surface targets for melanoma 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 melanoma | % positive | Internalizes | Clinical stage |
|---|---|---|---|---|---|
| 1 | MST1R macrophage stimulating 1 receptor | High (0.94) | 100% | yes | Clinical |
| 2 | HER3 (ERBB3) erb-b2 receptor tyrosine kinase 3 | High (0.90) | 100% | yes | Clinical |
| 3 | S1PR1 sphingosine-1-phosphate receptor 1 | High (0.69) | 100% | yes | Clinical |
| 4 | AMFR autocrine motility factor receptor | High (1.00) | 100% | yes | Discovery |
| 5 | c-MET (MET) MET proto-oncogene, receptor tyrosine kinase | High (0.67) | 100% | yes | Clinical |
| 6 | GPR139 G protein-coupled receptor 139 | High (0.97) | 100% | yes | Discovery |
| 7 | IGF1R insulin like growth factor 1 receptor | High (0.78) | 100% | yes | Clinical |
| 8 | NR3C2 nuclear receptor subfamily 3 group C member 2 | High (0.87) | 100% | uncertain | Clinical |
| 9 | TRPV2 transient receptor potential cation channel subfamily V member 2 | High (1.00) | 100% | uncertain | Discovery |
| 10 | RET ret proto-oncogene | High (0.92) | 100% | — | Clinical |
| 11 | HRH4 histamine receptor H4 | High (0.67) | 100% | yes | Clinical |
| 12 | AGTRAP angiotensin II receptor associated protein | High (0.81) | 100% | yes | Discovery |
| 13 | P2RX7 purinergic receptor P2X 7 | High (0.79) | 100% | uncertain | Clinical |
| 14 | CHRNA7 cholinergic receptor nicotinic alpha 7 subunit | High (0.69) | 83% | yes | Clinical |
| 15 | NOTCH2 notch receptor 2 | High (0.61) | 100% | yes | Clinical |
| 16 | SDCBP syndecan binding protein | High (1.00) | 100% | — | Discovery |
| 17 | CDK2 cyclin dependent kinase 2 | High (0.83) | 100% | — | Clinical |
| 18 | TNFRSF12A TNF receptor superfamily member 12A | High (0.92) | 100% | uncertain | Clinical |
| 19 | IL18R1 interleukin 18 receptor 1 | High (0.89) | 100% | uncertain | Clinical |
| 20 | RNF43 ring finger protein 43 | High (0.94) | 100% | — | Discovery |
| 21 | CSPG4 chondroitin sulfate proteoglycan 4 | High (0.97) | 100% | — | Discovery |
| 22 | FGFR1 fibroblast growth factor receptor 1 | High (0.53) | 90% | yes | Clinical |
| 23 | HMGA1 high mobility group AT-hook 1 | High (0.94) | 100% | — | Discovery |
| 24 | OXER1 oxoeicosanoid receptor 1 | High (0.87) | 100% | uncertain | Discovery |
| 25 | BRAF B-Raf proto-oncogene, serine/threonine kinase | High (0.97) | 100% | — | Clinical |
Internalizing receptors in melanoma
Targets expressed in melanoma 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:
MST1R · HER3 (ERBB3) · S1PR1 · AMFR · c-MET (MET) · GPR139 · IGF1R · HRH4 · AGTRAP · CHRNA7 · NOTCH2 · FGFR1
Melanoma targets already in clinical development
Targets with a clinical-stage drug program (any modality) that are also expressed in melanoma. Clinical precedent lowers development risk but usually means more competition:
MST1R · HER3 (ERBB3) · S1PR1 · c-MET (MET) · IGF1R · NR3C2 · RET · HRH4 · P2RX7 · CHRNA7 · NOTCH2 · CDK2
How these melanoma 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 melanoma, 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 melanoma targets against your own criteria: isotope, organ limits, novelty.
Run a free melanoma 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
- 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.