ERBB2
ERBB2 (erb-b2 receptor tyrosine kinase 2), also known as Human epidermal growth factor receptor 2 (HER2) (human EGFR 2), is a protein-coding gene that encodes a member of the ErbB family of receptor tyrosine kinases.
ERBB2 (erb-b2 receptor tyrosine kinase 2), also known as Human epidermal growth factor receptor 2 (HER2) (human EGFR 2), is a protein-coding gene that encodes a member of the ErbB family of receptor tyrosine kinases. The ERBB2 protein is a transmembrane receptor composed of an extracellular ligand-interaction region, a single membrane-spanning segment, and an intracellular tyrosine kinase domain. Unlike several related ErbB receptors, ERBB2 has no well-established high-affinity soluble ligand; it functions primarily as a preferred dimerization partner for ligand-activated receptors such as EGFR (ErbB1).
Dimerization activates ERBB2 kinase activity and promotes phosphorylation of intracellular Signaling proteins, including pathways involving RAS–MAPK and Phosphatidylinositol 3-kinase (PI3K)–Protein kinase B (PKB). These signals regulate cellular proliferation, survival, differentiation, migration, and tissue organization. Increased ERBB2 copy number or protein expression can produce persistent Signaling and is a clinically important molecular alteration in several Cancers, particularly breast cancer, as well as subsets of gastric, gastroesophageal, colorectal, lung, and other Tumors. ERBB2-directed therapies include monoclonal antibodies, antibody-drug conjugates, and small-molecule kinase inhibitors; the latter can inhibit ERBB2 alone or together with related receptors such as EGFR.
ERBB2 activity is influenced by interactions with the tumor microenvironment and with other oncogenic alterations, including changes involving PIK3CA, MET, MYC, and MDM2. Its expression or amplification may be evaluated using immunohistochemistry and fluorescence in situ hybridization, methods that distinguish increased protein abundance from increased gene copy number. ERBB2 Signaling has also been investigated beyond oncology, including in studies of respiratory syncytial virus and interleukin-17 family-associated processes.
Rebuilt from PubMed 18 Sept 2026 · no new papers today
Where the papers sit
15 papers study erbb2 directly. The themes below are drawn from those 15. 1 paradigm shift and 1 new direction follow.
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HER2 and EGFR Therapeutics : Targeting is expanding from kinase inhibitors toward vaccines, CAR-T cells and antibody-drug conjugates, while molecular profiling identifies actionable receptor alterations. Lapatinib also appears in antiviral repurposing. 9 papers · 60%
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HER2 Breast Cancer Targeting : HER2 treatment is moving beyond amplification toward precision radiotherapy with radiolabeled trastuzumab, including trastuzumab-resistant brain metastases. Exosome profiling may add blood-based disease characterization. 4 papers · 26.7%
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ErbB Receptors in Carcinoma : ErbB receptor expression is being linked to carcinoma grade and oncogenesis, while trastuzumab deruxtecan offers a way to overcome cetuximab resistance caused by an EGFR ectodomain mutation. 2 papers · 13.3%
Resistance to antibody blockade does not imply failure of further ErbB-directed treatment
The brain-metastatic HER2-positive breast-cancer model treated with trastuzumab and [¹⁷⁷Lu]Lu-DOTA-trastuzumab, and the EGFR S442-mutant colorectal and head-and-neck cancer models treated with cetuximab and trastuzumab deruxtecan, challenge the assumption that resistance to receptor-directed antibodies exhausts targeted therapy. In the breast-cancer model, lesions retained HER2 but became insensitive to trastuzumab, while radionuclide-linked trastuzumab caused DNA-damage-mediated killing regardless of trastuzumab sensitivity; in the EGFR-mutant models, cetuximab resistance was instead overcome by blocking the ErbB2 route with trastuzumab deruxtecan. Together, these findings shift the implication of resistance from abandonment of ErbB targeting to selection of a different cytotoxic mechanism or ErbB receptor node 42734882Sep 42176792May.
ERBB2-directed pharmacology is proposed as an antiviral strategy against respiratory syncytial virus
The A549-cell and BALB/c mouse models of respiratory syncytial virus infection treated with lapatinib place ErbB2 outside the set’s predominantly cancer-focused roles as a therapeutic target, biomarker, or immune-oncology antigen. Lapatinib suppressed RSV replication and inflammatory lung injury, and the abstract attributes this effect to targeting ErbB1 and ErbB2 and reducing IL-17 signaling; IL-17 overexpression antagonized the antiviral effect. This gives ERBB2 a distinct antiviral role and motivates repurposing ErbB2 inhibition for RSV disease rather than tumor control 42376990Jun.
Recent Findings on ERBB2
HER2 Cancer Biomarkers and Therapies: Bladder tumors showed that HER2 membrane expression and ERBB2 amplification represent distinct features, with amplification predicting poorer survival while HER2 immunohistochemistry scores lacked prognostic value 42732768Sep. Stepwise molecular profiling also identified actionable HER2 amplification and a co-occurring EGFR L858R mutation in non-small cell lung cancer, enabling sequential trastuzumab and gefitinib responses 42681853Sep. Preclinical strategies now span HER2-targeted antisense oligonucleotide delivery, antibody-drug conjugate linker design, and dual EGFR/HER-2 small-molecule inhibition 42715048Sep42218895May42217499May. HER2 ECD mRNA-LNP vaccination enhanced CD8+ tumor-infiltrating lymphocyte activity and showed greater efficacy with PD-1 immune checkpoint blockade or chemoradiotherapy, while CCL19-armed oncolytic adenovirus improved HER2 CAR-T cell recruitment in ovarian tumors 42378880Jun42250288Jun. Lapatinib additionally inhibited respiratory syncytial virus through ErbB1 and ErbB2 targeting and IL-17 downregulation, underscoring the varied biological uses of HER2-directed agents 42376990Jun.
HER2 Breast Cancer Targeting: Radiolabeled trastuzumab produced therapeutic activity in primary, metastatic, and brain HER2-positive breast cancer models, including trastuzumab-resistant brain metastases 42480146Jul42734882Sep. [177Lu]Lu-DOTA-trastuzumab caused DNA double-strand break-mediated cytotoxicity despite trastuzumab resistance, whereas [47Sc]Sc-NOTA-trastuzumab showed serum stability, HER2 specificity, therapeutic benefit, and increased M1-like macrophages 42734882Sep42480146Jul. Intracranial antibody delivery remained heterogeneous, and immuno-PET identified lesions with greater accessibility across a disrupted blood-brain barrier 42734882Sep. Precision selection is also expanding beyond amplification through HER2 mutations, HER2-directed tyrosine-kinase inhibitor combinations with trastuzumab, and exosome profiling that distinguished HER2-positive breast cancer from other subtypes 42423636Jul42410964Jul.
ErbB Signaling in Carcinoma: Clear cell renal cell carcinoma showed frequent nuclear HER2/ErbB3 co-expression, which correlated with higher Fuhrman Nuclear Grade and advanced clinical stage after heregulin-induced nuclear translocation 42674699Aug. In colorectal and head and neck cancer models, the EGFR S442 ectodomain mutation weakened cetuximab binding and caused resistance, while trastuzumab deruxtecan overcame resistance through physical EGFR–ERBB2 interaction 42176792May. These findings support nuclear HER2/ErbB3 complexes as prognostic biomarkers and ERBB2 blockade as a strategy against mutation-driven EGFR therapy resistance.
Written from 15 PubMed abstracts, each one cited by PMID above. Published: 2026-08-20. Last written: 2026-09-16 by GPT. Drafted by language models from published abstracts; not medical advice.