HER2 (ERBB2) as a Radioligand Therapy Target
HER2 (ERBB2), erb-b2 receptor tyrosine kinase 2, is a cell-surface protein (RTK). In Human Protein Atlas immunohistochemistry, HER2 staining is highest in breast cancer (64% of samples positive), bladder cancer (58% of samples positive) and head and neck cancer (25% of samples positive). Published literature reports that HER2 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Clinical-stage (up to phase 3, any modality).
Is HER2 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 breast cancer, 64% 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.
HER2 expression in cancer
Protein expression of HER2 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 |
|---|---|---|---|
| Breast Cancer | 0.52 | High | 64% |
| Bladder Cancer | 0.33 | Medium | 58% |
| Head and Neck Cancer | 0.25 | Medium | 25% |
| Colorectal Cancer | 0.24 | Medium | 46% |
| Liver Cancer | 0.19 | Low | 58% |
| Pancreatic Cancer | 0.18 | Low | 46% |
| Ovarian Cancer | 0.18 | Low | 27% |
| Endometrial Cancer | 0.14 | Low | 33% |
| Skin Cancer | 0.11 | Low | 33% |
| Gastric Cancer | 0.11 | Low | 17% |
| Lung Cancer | 0.09 | Low | 18% |
| Testicular Cancer | 0.07 | Low | 22% |
| Kidney Cancer | 0.06 | Low | 17% |
| Cervical Cancer | 0.03 | Low | 10% |
| Melanoma | 0.03 | Low | 9% |
Not detected by IHC in: lymphoma, thyroid cancer, neuroendocrine tumors, prostate cancer, glioma.
Is HER2 internalized?
Yes. The compact vNAR-based immunoconjugates support efficient receptor recognition, internalization, and intracellular trafficking, features rarely achieved by conventional IgG antibodies.
Sources: PMID 42075887 · PMID 41628581 · PMID 41212147 · PMID 40736405 · PMID 40052543. AI-extracted from abstracts, so verify before citing.
HER2 clinical trials
Clinical-stage (up to phase 3, any modality). Nuclens hasn't indexed trials for HER2 yet. Search ClinicalTrials.gov for HER2 trials.
HER2 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 HER2 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
HER2 gene essentiality (DepMap)
CRISPR knockout effect across 1258 cancer cell lines: -0.35 (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 breast cancer radioligand targets
HER3 (ERBB3) · c-MET (MET) · FAP · STEAP2 · EGFR · B7-H3 (CD276) · SSTR2 · ITGAV
See all radioligand therapy targets in breast cancer.
See how HER2 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.