HER3 (ERBB3)
A receptor on the surface of most lung cancer cells that helps tumours resist treatment. Drugs aimed at it exist, but measuring how much of it a tumour carries has so far failed to predict who benefits.
Overview
HER3 is a member of the epidermal growth factor receptor family with impaired intrinsic kinase activity, signalling instead through heterodimerisation with HER2 and EGFR and driving the PI3K-AKT pathway. It is widely expressed in epithelial cancers and is upregulated after EGFR tyrosine-kinase inhibitor treatment, which is why it became a target for antibody-drug conjugates in EGFR-mutant lung cancer. One published series reported HER3 expression in 83% of non-small cell lung cancers, with overexpression in 42% of a 45-patient cohort, more often than HER2.
The target's problem is measurement, not prevalence. Reviews state that there are no validated HER3 immunohistochemistry assays and no standardised scoring thresholds for predicting benefit, and the sponsor's own biomarker analyses of patritumab deruxtecan report no relationship between efficacy and HER3 protein expression by immunohistochemistry. An mRNA-based alternative developed by the SOLTI group found activity across a wide range of ERBB3 expression, again suggesting limited predictive value.
For molecular imaging this matters directly. Three antibody PET tracers have been built against HER3 (64Cu-patritumab, 89Zr-GSK2849330 and 89Zr-lumretuzumab) and all three belong to therapeutic programmes that were discontinued or lost momentum; in one published study no correlation between tumour uptake and ex-vivo immunohistochemistry could be determined. A single imaging trial is currently recruiting, 89Zr-patritumab deruxtecan at the Netherlands Cancer Institute with Daiichi Sankyo, on the rationale that HER3 expression can be assessed non-invasively including at sites that are difficult to biopsy.
- 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 receptor on the surface of most lung cancer cells that helps tumours resist treatment. Drugs aimed at it exist, but measuring how much of it a tumour carries has so far failed to predict who benefits.
- 1 · What it is
A receptor on the surface of most lung cancer cells that helps tumours resist treatment. Drugs aimed at it exist, but measuring how much of it a tumour carries has so far failed to predict who benefits.
- 2 · What goes wrong in cancer
A receptor tyrosine kinase of the EGFR family with negligible intrinsic catalytic activity, which signals by heterodimerising with HER2 or EGFR to activate PI3K-AKT.
- 3 · How drugs use it
No product in this corpus aims at HER3 (ERBB3) 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
Biology
A receptor tyrosine kinase of the EGFR family with negligible intrinsic catalytic activity, which signals by heterodimerising with HER2 or EGFR to activate PI3K-AKT. Its expression rises after EGFR inhibition, making it a mechanism of acquired resistance as well as a target.
- Non-small cell lung cancer: reported in 83% of cases, with overexpression in 42% of one 45-patient cohort
- Breast cancer, including after endocrine and HER2-directed therapy
- Colorectal and other epithelial cancers
- Upregulated in tumours progressing on EGFR tyrosine-kinase inhibitors
How often this target appears
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Non-small cell lung cancer | 83% | immunohistochemistry, any expression, published series | PMC |
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:"HER3" OR ABSTRACT:"HER3" OR TITLE:"ERBB3" OR ABSTRACT:"ERBB3" OR TITLE:"erb-b2 receptor tyrosine kinase 3" OR ABSTRACT:"erb-b2 receptor tyrosine kinase 3") 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 HER3 (ERBB3), not a curated reading list.
Similar pages
not linked directly; found by shared links- TargetIntegrin αvβ3
Shares Non-small cell lung cancer, Copper-64.
- TargetClaudin-18.2
Shares HER2 and the tag adc-target.
- IndicationSmall-cell lung cancer
Shares Non-small cell lung cancer and the tag lung.
- OpportunityDLL3 imaging for small-cell lung cancer
Shares Zirconium-89 and the tag lung.
- PersonJason S. Lewis
Shares HER2, Zirconium-89.
- TechnologyAutomated synthesis modules
Shares Zirconium-89, Copper-64.
- TechnologyHER2 PET
Shares HER2, Zirconium-89.
- IndicationLung neuroendocrine tumours (typical and atypical carcinoid)
Shares Non-small cell lung cancer and the tag lung.