EPHA3 as a Radioligand Therapy Target
EPHA3, EPH receptor A3, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, EPHA3 staining is highest in testicular cancer (100% of samples positive), glioma (100% of samples positive) and cervical cancer (100% of samples positive). Published literature reports that EPHA3 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Discovery-stage (no clinical drug program).
Is EPHA3 a good radioligand therapy target?
Scored against the six criteria that decide whether a protein can become a radioligand therapy:
- ✅ Cell-surface accessibility: Localized to the cell surface, so a radioligand can reach it from circulation.
- ✅ Tumor expression: High IHC staining in testicular cancer, 100% of samples positive.
- ✅ Internalization: Reported to internalize, which favors radionuclide retention.
- ⚠️ Clinical precedent: Discovery-stage (no clinical drug program)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
EPHA3 expression in cancer
Protein expression of EPHA3 across 20 cancer types from Human Protein Atlas immunohistochemistry. The score is a weighted staining intensity from 0 to 1; "% positive" is the share of patient samples with detectable staining.
| Cancer type | IHC score | Level | % positive |
|---|---|---|---|
| Testicular Cancer | 0.52 | High | 100% |
| Glioma | 0.47 | Medium | 100% |
| Cervical Cancer | 0.42 | Medium | 100% |
| Kidney Cancer | 0.42 | Medium | 100% |
| Prostate Cancer | 0.39 | Medium | 91% |
| Melanoma | 0.39 | Medium | 100% |
| Bladder Cancer | 0.33 | Medium | 100% |
| Endometrial Cancer | 0.33 | Medium | 91% |
| Ovarian Cancer | 0.31 | Medium | 92% |
| Gastric Cancer | 0.31 | Medium | 92% |
| Breast Cancer | 0.31 | Medium | 83% |
| Colorectal Cancer | 0.30 | Medium | 91% |
| Pancreatic Cancer | 0.28 | Medium | 83% |
| Liver Cancer | 0.27 | Medium | 82% |
| Head and Neck Cancer | 0.25 | Medium | 75% |
| Skin Cancer | 0.19 | Low | 58% |
| Lung Cancer | 0.19 | Low | 58% |
| Thyroid Cancer | 0.17 | Low | 50% |
| Lymphoma | 0.11 | Low | 33% |
Not detected by IHC in: neuroendocrine tumors.
Is EPHA3 internalized?
Yes. ephrin-A1 and ephrin-A5 exhibit tumor-suppressive properties by promoting receptor internalization and degradation
Sources: PMID 41200151 · PMID 27807832 · PMID 21135139. AI-extracted from abstracts, so verify before citing.
EPHA3 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for EPHA3 yet. Search ClinicalTrials.gov for EPHA3 trials.
EPHA3 normal tissue expression
Normal-tissue expression in dose-limiting organs (kidney, liver, bone marrow, salivary glands) drives radioligand dosimetry risk. Nuclens is re-validating its normal-tissue values, so they are not shown here yet. See EPHA3 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
EPHA3 gene essentiality (DepMap)
CRISPR knockout effect across 1256 cancer cell lines: -0.05 (not essential). Radioligands kill by radiation, not by blocking the target, so essentiality matters less than for inhibitors. A non-essential target can still be an excellent radioligand target.
Related testicular cancer radioligand targets
HER3 (ERBB3) · c-MET (MET) · STEAP2 · KIT · SSTR2 · TMEFF2 · Mesothelin (MSLN) · HER2 (ERBB2)
See all radioligand therapy targets in testicular cancer.
See how EPHA3 ranks against 15,000 targets for your indication.
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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.