ERBB4 as a Radioligand Therapy Target
ERBB4, erb-b2 receptor tyrosine kinase 4, is a cell-surface protein (RTK). In Human Protein Atlas immunohistochemistry, ERBB4 staining is highest in testicular cancer (100% of samples positive), skin cancer (82% of samples positive) and head and neck cancer (75% of samples positive). Evidence on whether ERBB4 internalizes is mixed. Clinical status: Clinical-stage (up to phase 3, any modality).
Is ERBB4 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: Mixed evidence.
- ✅ 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.
ERBB4 expression in cancer
Protein expression of ERBB4 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 | 0.61 | High | 100% |
| Skin Cancer | 0.42 | Medium | 82% |
| Head and Neck Cancer | 0.42 | Medium | 75% |
| Bladder Cancer | 0.42 | Medium | 75% |
| Ovarian Cancer | 0.39 | Medium | 75% |
| Kidney Cancer | 0.33 | Medium | 75% |
| Thyroid Cancer | 0.33 | Medium | 75% |
| Liver Cancer | 0.33 | Medium | 75% |
| Endometrial Cancer | 0.33 | Medium | 73% |
| Melanoma | 0.33 | Medium | 67% |
| Pancreatic Cancer | 0.33 | Medium | 58% |
| Colorectal Cancer | 0.28 | Medium | 67% |
| Prostate Cancer | 0.28 | Medium | 58% |
| Breast Cancer | 0.28 | Medium | 50% |
| Lung Cancer | 0.27 | Medium | 64% |
| Neuroendocrine Tumors | 0.25 | Medium | 75% |
| Cervical Cancer | 0.22 | Medium | 50% |
| Gastric Cancer | 0.18 | Low | 55% |
| Glioma | 0.17 | Low | 42% |
| Lymphoma | 0.11 | Low | 25% |
Is ERBB4 internalized?
Uncertain. The provided abstract does not specifically mention whether ERBB4 undergoes internalization or endocytosis upon ligand/antibody binding. It discusses the effects of inhibitors on the ErbB family but lacks details on receptor trafficking.
Sources: PMID 37581931 · PMID 36584483 · PMID 26027736 · PMID 25349163 · PMID 25102001. AI-extracted from abstracts, so verify before citing.
ERBB4 clinical trials
Clinical-stage (up to phase 3, any modality). Nuclens hasn't indexed trials for ERBB4 yet. Search ClinicalTrials.gov for ERBB4 trials.
ERBB4 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 ERBB4 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
ERBB4 gene essentiality (DepMap)
CRISPR knockout effect across 1254 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 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.
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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.