EPHA4 as a Radioligand Therapy Target
EPHA4, EPH receptor A4, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, EPHA4 staining is highest in thyroid cancer (100% of samples positive), bladder cancer (64% of samples positive) and testicular cancer (42% of samples positive). Published literature reports that EPHA4 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Discovery-stage (no clinical drug program).
Is EPHA4 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 thyroid 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.
EPHA4 expression in cancer
Protein expression of EPHA4 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 |
|---|---|---|---|
| Thyroid Cancer | 1.00 | High | 100% |
| Bladder Cancer | 0.36 | Medium | 64% |
| Testicular Cancer | 0.17 | Low | 42% |
| Neuroendocrine Tumors | 0.17 | Low | 25% |
| Skin Cancer | 0.15 | Low | 27% |
| Endometrial Cancer | 0.15 | Low | 27% |
| Pancreatic Cancer | 0.12 | Low | 27% |
| Gastric Cancer | 0.06 | Low | 9% |
| Breast Cancer | 0.06 | Low | 8% |
| Lung Cancer | 0.03 | Low | 10% |
| Glioma | 0.03 | Low | 9% |
| Liver Cancer | 0.03 | Low | 9% |
| Ovarian Cancer | 0.03 | Low | 8% |
| Cervical Cancer | 0.03 | Low | 8% |
Not detected by IHC in: colorectal cancer, head and neck cancer, lymphoma, melanoma, kidney cancer, prostate cancer.
Is EPHA4 internalized?
Yes. ephrin-A1 and ephrin-A5 exhibit tumor-suppressive properties by promoting receptor internalization and degradation.
Sources: PMID 41200151 · PMID 32745487 · PMID 27323967 · PMID 26176328 · PMID 22916121. AI-extracted from abstracts, so verify before citing.
EPHA4 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for EPHA4 yet. Search ClinicalTrials.gov for EPHA4 trials.
EPHA4 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 EPHA4 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
EPHA4 gene essentiality (DepMap)
CRISPR knockout effect across 1256 cancer cell lines: 0.08 (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 thyroid cancer radioligand targets
c-MET (MET) · HER3 (ERBB3) · EPCAM · SSTR2 · EGFR · ITGAV · STEAP2 · FAP
See all radioligand therapy targets in thyroid cancer.
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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.