EPHA8 as a Radioligand Therapy Target
EPHA8, EPH receptor A8, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, EPHA8 staining is highest in thyroid cancer (75% of samples positive), liver cancer (55% of samples positive) and breast cancer (42% of samples positive). Published literature reports that EPHA8 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Discovery-stage (no clinical drug program).
Is EPHA8 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: Medium IHC staining in thyroid cancer, 75% 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.
EPHA8 expression in cancer
Protein expression of EPHA8 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 | 0.42 | Medium | 75% |
| Liver Cancer | 0.30 | Medium | 55% |
| Breast Cancer | 0.19 | Low | 42% |
| Melanoma | 0.17 | Low | 33% |
| Bladder Cancer | 0.15 | Low | 27% |
| Colorectal Cancer | 0.14 | Low | 33% |
| Prostate Cancer | 0.14 | Low | 33% |
| Ovarian Cancer | 0.11 | Low | 25% |
| Testicular Cancer | 0.08 | Low | 25% |
| Lung Cancer | 0.06 | Low | 18% |
| Pancreatic Cancer | 0.06 | Low | 18% |
| Glioma | 0.06 | Low | 18% |
| Gastric Cancer | 0.06 | Low | 17% |
| Lymphoma | 0.03 | Low | 9% |
| Endometrial Cancer | 0.03 | Low | 8% |
Not detected by IHC in: skin cancer, head and neck cancer, kidney cancer, neuroendocrine tumors, cervical cancer.
Is EPHA8 internalized?
Yes. EphA8 undergoes clathrin-mediated endocytosis upon treatment with ephrin-A5.
Sources: PMID 21343910 · PMID 20496116. AI-extracted from abstracts, so verify before citing.
EPHA8 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for EPHA8 yet. Search ClinicalTrials.gov for EPHA8 trials.
EPHA8 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 EPHA8 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
EPHA8 gene essentiality (DepMap)
CRISPR knockout effect across 1240 cancer cell lines: 0.04 (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.