Radioligand Therapy Targets in Testicular Cancer
We screened every cell-surface protein with tumor immunohistochemistry data in testicular cancer (including testicular germ cell tumors). 4,013 show detectable protein staining. Established and emerging radioligand targets expressed in testicular cancer include HER3 (ERBB3), STEAP2, c-MET (MET) and KIT. Below, we rank every candidate by tumor expression, internalization and clinical maturity.
Established and emerging radioligand targets in testicular cancer
Targets already pursued with radioligands or other targeted modalities that show protein expression in testicular cancer:
| Target | IHC in testicular cancer | % positive | Internalizes |
|---|---|---|---|
| HER3 (ERBB3) | High (0.87) | 100% | yes |
| STEAP2 | High (0.64) | 100% | — |
| c-MET (MET) | High (0.52) | 100% | yes |
| KIT | Medium (0.39) | 50% | no |
| B7-H3 (CD276) | Medium (0.33) | 80% | — |
| TMEFF2 | Medium (0.33) | 80% | — |
| EPCAM | Low (0.17) | 40% | — |
| Nectin-4 (NECTIN4) | Low (0.15) | 36% | no |
| FAP | Low (0.14) | 42% | yes |
| Claudin 18.2 (CLDN18) | Low (0.12) | 27% | uncertain |
| SSTR2 | Low (0.11) | 25% | yes |
| HER2 (ERBB2) | Low (0.07) | 22% | yes |
| CD38 | Low (0.07) | 20% | — |
| ITGB6 | Low (0.07) | 20% | — |
| DLK1 | Low (0.06) | 9% | — |
| Mesothelin (MSLN) | Low (0.06) | 8% | yes |
Top cell-surface targets for testicular 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 testicular cancer | % positive | Internalizes | Clinical stage |
|---|---|---|---|---|---|
| 1 | HER3 (ERBB3) erb-b2 receptor tyrosine kinase 3 | High (0.87) | 100% | yes | Clinical |
| 2 | IGF1R insulin like growth factor 1 receptor | High (0.85) | 100% | yes | Clinical |
| 3 | GPR139 G protein-coupled receptor 139 | High (1.00) | 100% | yes | Discovery |
| 4 | PTPN13 protein tyrosine phosphatase non-receptor type 13 | High (0.97) | 100% | yes | Discovery |
| 5 | AMFR autocrine motility factor receptor | High (0.97) | 100% | yes | Discovery |
| 6 | NR3C2 nuclear receptor subfamily 3 group C member 2 | High (0.89) | 100% | uncertain | Clinical |
| 7 | NOTCH1 notch receptor 1 | High (0.70) | 100% | yes | Clinical |
| 8 | IL1R2 interleukin 1 receptor type 2 | High (0.69) | 100% | yes | Discovery |
| 9 | FZD6 frizzled class receptor 6 | High (0.87) | 100% | yes | Discovery |
| 10 | M6PR mannose-6-phosphate receptor, cation dependent | High (0.87) | 100% | yes | Discovery |
| 11 | S1PR1 sphingosine-1-phosphate receptor 1 | Medium (0.48) | 100% | yes | Clinical |
| 12 | FZD3 frizzled class receptor 3 | High (0.85) | 100% | yes | Discovery |
| 13 | AGTRAP angiotensin II receptor associated protein | High (0.83) | 100% | yes | Discovery |
| 14 | NOTCH2 notch receptor 2 | High (0.64) | 100% | yes | Clinical |
| 15 | EPHB2 EPH receptor B2 | High (0.92) | 100% | uncertain | Discovery |
| 16 | c-MET (MET) MET proto-oncogene, receptor tyrosine kinase | High (0.52) | 100% | yes | Clinical |
| 17 | CHRNA7 cholinergic receptor nicotinic alpha 7 subunit | High (0.61) | 100% | yes | Clinical |
| 18 | CSPG4 chondroitin sulfate proteoglycan 4 | High (1.00) | 100% | — | Discovery |
| 19 | TNFRSF12A TNF receptor superfamily member 12A | High (0.92) | 100% | uncertain | Clinical |
| 20 | GPER1 G protein-coupled estrogen receptor 1 | High (0.78) | 92% | yes | Discovery |
| 21 | VIPR1 vasoactive intestinal peptide receptor 1 | High (0.56) | 100% | yes | Discovery |
| 22 | HRH4 histamine receptor H4 | High (0.58) | 100% | yes | Clinical |
| 23 | GFRA3 GDNF family receptor alpha 3 | High (0.89) | 100% | uncertain | Discovery |
| 24 | ADRM1 ADRM1 26S proteasome ubiquitin receptor | High (0.86) | 100% | uncertain | Clinical |
| 25 | BDKRB1 bradykinin receptor B1 | High (0.89) | 100% | uncertain | Clinical |
Internalizing receptors in testicular cancer
Targets expressed in testicular 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) · IGF1R · GPR139 · PTPN13 · AMFR · NOTCH1 · IL1R2 · FZD6 · M6PR · S1PR1 · FZD3 · AGTRAP
Testicular Cancer targets already in clinical development
Targets with a clinical-stage drug program (any modality) that are also expressed in testicular cancer. Clinical precedent lowers development risk but usually means more competition:
HER3 (ERBB3) · IGF1R · NR3C2 · NOTCH1 · S1PR1 · NOTCH2 · c-MET (MET) · CHRNA7 · TNFRSF12A · HRH4 · ADRM1 · BDKRB1
How these testicular 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 testicular 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 testicular cancer targets against your own criteria: isotope, organ limits, novelty.
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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.