{"entity":{"id":"her3","kind":"target","name":"HER3 (ERBB3)","aka":["ERBB3","erb-b2 receptor tyrosine kinase 3"],"tldr":"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.","summary":"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.\n\nThe 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.\n\nFor 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.","asOf":"2026-09-23","links":[{"label":"HER3 expression in non-small cell lung cancer","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12393064/"},{"label":"No relationship between HER3-DXd efficacy and HER3 immunohistochemistry, Nature Communications 2024","url":"https://www.nature.com/articles/s41467-024-50056-y"},{"label":"No validated HER3 assays or scoring thresholds (review)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12758208/"},{"label":"NCT06222489: 89Zr-patritumab deruxtecan PET/CT","url":"https://clinicaltrials.gov/study/NCT06222489"}],"tags":["adc-target","resistance","lung"],"related":["her2","opp-her3-imaging-crossover","cu-64","zr-89"],"indications":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"ERBB3","hgnc":"HGNC:3431","ensembl":"ENSG00000065361","uniprot":"P21860","entrez":"2065","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.","whereFound":["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"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"nsclc","pct":83,"measure":"immunohistochemistry, any expression, published series","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12393064/"}]},"route":"/targets/her3/","neighbours":{"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"opportunity":[{"id":"opp-her3-imaging-crossover","kind":"opportunity","name":"HER3 imaging, and why three tracers stalled","route":"/opportunities/opp-her3-imaging-crossover/"}],"isotope":[{"id":"cu-64","kind":"isotope","name":"Copper-64","route":"/isotopes/cu-64/"},{"id":"zr-89","kind":"isotope","name":"Zirconium-89","route":"/isotopes/zr-89/"}],"indication":[{"id":"nsclc","kind":"indication","name":"Non-small cell lung cancer","route":"/indications/nsclc/"}]}}