EGFR as a Radioligand Therapy Target
EGFR, epidermal growth factor receptor, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, EGFR staining is highest in head and neck cancer (100% of samples positive), liver cancer (100% of samples positive) and kidney cancer (100% of samples positive). Published literature reports that EGFR internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Clinical-stage (up to phase 3, any modality), with 1 active clinical trial.
Is EGFR 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 head and neck cancer, 100% of samples positive.
- ✅ Internalization: Reported to internalize, which favors radionuclide retention.
- ✅ Clinical precedent: Clinical-stage (up to phase 3, any modality)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
EGFR expression in cancer
Protein expression of EGFR 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 |
|---|---|---|---|
| Head and Neck Cancer | 1.00 | High | 100% |
| Liver Cancer | 0.88 | High | 100% |
| Kidney Cancer | 0.85 | High | 100% |
| Glioma | 0.81 | High | 92% |
| Bladder Cancer | 0.79 | High | 100% |
| Skin Cancer | 0.75 | High | 100% |
| Pancreatic Cancer | 0.64 | High | 100% |
| Lung Cancer | 0.63 | High | 80% |
| Cervical Cancer | 0.61 | High | 92% |
| Endometrial Cancer | 0.48 | Medium | 73% |
| Colorectal Cancer | 0.44 | Medium | 83% |
| Prostate Cancer | 0.39 | Medium | 67% |
| Gastric Cancer | 0.36 | Medium | 73% |
| Thyroid Cancer | 0.33 | Medium | 50% |
| Breast Cancer | 0.17 | Low | 30% |
| Ovarian Cancer | 0.11 | Low | 25% |
Not detected by IHC in: lymphoma, melanoma, neuroendocrine tumors, testicular cancer.
Is EGFR internalized?
Yes. In recent studies, we showed that gefitinib...induces a massive, non-physiological endocytosis of EGFR, known as gefitinib-mediated endocytosis (GME), in different glioblastoma cell lines.
Sources: PMID 42390764 · PMID 42380284 · PMID 42364810 · PMID 42335400 · PMID 42333517. AI-extracted from abstracts, so verify before citing.
EGFR clinical trials
Clinical-stage (up to phase 3, any modality). 1 active trial reference EGFR (ClinicalTrials.gov, accessed 2026-09-28).
EGFR 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 EGFR in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
EGFR gene essentiality (DepMap)
CRISPR knockout effect across 1258 cancer cell lines: -0.24 (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 head and neck cancer radioligand targets
c-MET (MET) · HER3 (ERBB3) · ITGAV · SSTR2 · B7-H3 (CD276) · STEAP2 · Mesothelin (MSLN) · CEA (CEACAM5)
See all radioligand therapy targets in head and neck 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.