HER2
A growth-signal receptor. Some cancers make far too much of it, and drugs that block it or use it as a docking site have transformed those cancers.
Overview
Human epidermal growth factor receptor 2 is a receptor tyrosine kinase amplified in ~15-20% of breast cancers and a subset of gastric, colorectal, lung (mutations), and biliary cancers. Trastuzumab (1998) was the first targeted antibody in solid tumours. Trastuzumab deruxtecan redefined the target by working in 'HER2-low' tumours that older drugs ignored, and in 2026 gained approval in early-stage disease.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · A growth-signal receptor. Some cancers make far too much of it, and drugs that block it or use it as a docking site have transformed those cancers.
- 1 · What it is
A growth-signal receptor. Some cancers make far too much of it, and drugs that block it or use it as a docking site have transformed those cancers.
- 2 · What goes wrong in cancer
Ligand-less receptor that heterodimerises with HER3/EGFR to drive PI3K and MAPK signalling. Amplification is a true oncogenic driver; low expression is merely a delivery address for ADCs.
- 3 · How drugs use it
No product in this corpus aims at HER2 yet. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
External identifiers
Mutation hotspots
Companion diagnostics
- HercepTest · IHC 3+ (or 2+ confirmed by ISH) for trastuzumab; IHC 1+ or 2+/ISH-negative (HER2-low) for trastuzumab deruxtecan; IHC 0 with faint membrane staining (HER2-ultralow) for trastuzumab deruxtecan in HR-positive breast cancer
- PATHWAY anti-HER2/neu (4B5) · IHC 3+ (HER2-positive); IHC 1+ or 2+/ISH-negative (HER2-low) for trastuzumab deruxtecan; IHC 3+ solid tumours for tumour-agnostic trastuzumab deruxtecan
- HER2 IQFISH pharmDx and INFORM HER2 Dual ISH · HER2/CEP17 ratio at least 2.0, or ratio below 2.0 with average HER2 copy number at least 6.0 (ASCO/CAP 2018)
- FoundationOne CDx · Per companion claim: EGFR, ALK, BRAF V600, ERBB2 amplification, KRAS wild-type, BRCA1/2 and HRR genes, PIK3CA, MET exon 14, RET, FGFR2 fusions, IDH1, NTRK fusions; MSI-high; TMB at least 10 mutations per megabase
- Guardant360 CDx · Per companion claim: EGFR (osimertinib), EGFR exon 20 insertions (amivantamab), KRAS G12C (sotorasib), ESR1 mutations (elacestrant), ERBB2 mutations (zongertinib); negative plasma reflexes to tissue
Biology
Ligand-less receptor that heterodimerises with HER3/EGFR to drive PI3K and MAPK signalling. Amplification is a true oncogenic driver; low expression is merely a delivery address for ADCs.
- HER2+ breast cancer (~15-20%)
- HER2-low breast cancer (~50%)
- Gastric/GEJ (~15-20%)
- HER2-mutant NSCLC (~2-3%)
- Colorectal (~3-5%)
- Biliary tract
How often this target appears
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| HER2-positive breast cancer | 100% | IHC 3+ or ISH-amplified (defining) | Nature |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Latest papers
topQuery for this target: (TITLE:"HER2" OR ABSTRACT:"HER2" OR TITLE:"ERBB2" OR ABSTRACT:"ERBB2") AND (radiopharmaceutical OR radioligand OR radionuclide OR theranostic OR "nuclear medicine" OR "molecular imaging" OR radiotracer OR scintigraphy OR cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about HER2, not a curated reading list.
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