HER3 (ERBB3) as a Radioligand Therapy Target
HER3 (ERBB3), erb-b2 receptor tyrosine kinase 3, is a cell-surface protein (RTK). In Human Protein Atlas immunohistochemistry, HER3 staining is highest in gastric cancer (100% of samples positive), breast cancer (100% of samples positive) and melanoma (100% of samples positive). Published literature reports that HER3 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Clinical-stage (up to phase 3, any modality).
Is HER3 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 gastric 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.
HER3 expression in cancer
Protein expression of HER3 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 |
|---|---|---|---|
| Gastric Cancer | 0.93 | High | 100% |
| Breast Cancer | 0.91 | High | 100% |
| Melanoma | 0.90 | High | 100% |
| Pancreatic Cancer | 0.88 | High | 100% |
| Colorectal Cancer | 0.87 | High | 100% |
| Testicular Cancer | 0.87 | High | 100% |
| Bladder Cancer | 0.83 | High | 100% |
| Endometrial Cancer | 0.82 | High | 100% |
| Head and Neck Cancer | 0.75 | High | 100% |
| Neuroendocrine Tumors | 0.75 | High | 100% |
| Glioma | 0.75 | High | 100% |
| Ovarian Cancer | 0.73 | High | 100% |
| Kidney Cancer | 0.72 | High | 100% |
| Cervical Cancer | 0.72 | High | 100% |
| Prostate Cancer | 0.72 | High | 100% |
| Lung Cancer | 0.70 | High | 100% |
| Liver Cancer | 0.70 | High | 91% |
| Thyroid Cancer | 0.67 | High | 100% |
| Skin Cancer | 0.60 | High | 100% |
| Lymphoma | 0.31 | Medium | 67% |
Is HER3 internalized?
Yes. In vitro studies showed that the amount of payload released from cells after HER3-DXd treatment was associated with baseline HER3 expression levels, HER3 internalization rate, and turnover rate.
Sources: PMID 41752065 · PMID 41200151 · PMID 40174661 · PMID 38632563 · PMID 35740315. AI-extracted from abstracts, so verify before citing.
HER3 clinical trials
Clinical-stage (up to phase 3, any modality). Nuclens hasn't indexed trials for HER3 yet. Search ClinicalTrials.gov for HER3 trials.
HER3 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 HER3 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
HER3 gene essentiality (DepMap)
CRISPR knockout effect across 1258 cancer cell lines: -0.21 (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 gastric cancer radioligand targets
c-MET (MET) · FAP · EGFR · SSTR2 · CEA (CEACAM5) · Mesothelin (MSLN) · STEAP2 · B7-H3 (CD276)
See all radioligand therapy targets in gastric cancer.
See how HER3 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.