ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2024
Prevalence and Therapeutic Targeting of High-Level ERBB2 Amplification in NSCLC.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 19 citations in OpenAlex.
- Clinicopathological features and prognoses of HER-2-positive gastric cancer.Molecular and clinical oncology · 2026Article
- Association of Increased MIEN1 Copy Number With Worse Outcomes in Lung Adenocarcinoma and Cervical Cancer.Cureus · 2026Article
- Endometrial Cancer by ERBB2 Amplification (ERBB2amp) Status: Differences in Molecular Subtypes, Ancestry, and Real-World Outcomes.JCO precision oncology · 2026Article
- HER2 Alterations in Squamous Cell Lung Cancer: Biology, Therapeutic Landscape, and Emerging Precision Approaches.Cancers · 2026Review
- [Trastuzumab Deruxtecan for EGFR-mutant Lung Adenocarcinoma with Acquired High-level HER2 Amplification: A Case Report].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Article
- Review
- Association between tumor genomic mutations and the risk of PD-1 inhibitor-induced hypophysitis: a retrospective cohort study.Frontiers in endocrinology · 2026Article
- Tiered Group of Disease Driven Oncogene Informs Survival Outcome of Taiwanese and Japanese Patients with Advanced NSCLC in the LC-SCRUM-Asia Study.Lung Cancer (Auckland, N.Z.) · 2026Article
- HER2 amplification as a resistance mechanism to osimertinib and its successful treatment with trastuzumab deruxtecan: a case report.Frontiers in oncology · 2026Article
- Recent Advances in the Development and Clinical Use of HER2 Inhibitors in Non-Small Cell Lung Cancer.Biomolecules · 2025Review
- Comprehensive identification of NRG1 fusions in 25,203 patients with solid tumors.NPJ precision oncology · 2025Article
- Molecular landscape of HER2-mutated non-small cell lung cancer in Northeastern Brazil: Clinical, histopathological, and genomic insights.Oncotarget · 2025Article
- Triglyceride-glucose index in predicting gastric cancer prognosis: A need for caution.World journal of gastroenterology · 2025Article
- Light on the horizon for HER2 overexpressing non-small cell lung cancer?Translational lung cancer research · 2025Article
- Review
- Case Report: Trastuzumab deruxtecan plus toripalimab in ERBB2-amplified cervical mucosal melanoma.Frontiers in oncology · 2025Article
- Immunoconjugates as an Efficient Platform for Drug Delivery: A Resurgence of Natural Products in Targeted Antitumor Therapy.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Review
- Efficacy of disitamab vedotin in non-small cell lung cancer withFrontiers in oncology · 2024Article
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16 authors at 5 institutions in 2 countries.
Funding
Abstract
introductionERBB2 amplification in lung cancer remains poorly characterized. HER2 (encoded by ERBB2) is a transmembrane tyrosine kinase capable of ligand-independent dimerization and signaling when overexpressed, and a common cause of HER2 overexpression is ERBB2 amplification. Here, we evaluated the clinicopathologic and genomic characteristics of ERBB2-amplified NSCLC and explored a HER2 antibody-drug conjugate (ADC) therapeutic strategy.
methodsOur institutional next-generation DNA sequencing data (OncoPanel) from 5769 NSCLC samples (5075 patients) were queried for cases having high-level ERBB2 amplification (≥6 copies). Clinical and demographic characteristics were extracted from the electronic medical records. Efficacy of the pan-ERBB inhibitor afatinib or HER2 ADCs (trastuzumab deruxtecan and trastuzumab emtansine) was evaluated in NSCLC preclinical models and patients with ERBB2 amplification.
resultsHigh-level ERBB2 amplification was identified in 0.9% of lung adenocarcinomas and reliably predicted overexpression of HER2. ERBB2 amplification events are detected in two distinct clinicopathologic and genomic subsets of NSCLC: as the sole mitogenic driver in tumors arising in patients with a smoking history or as a concomitant alteration with other mitogenic drivers in patients with a light or never smoking history. We further reveal that trastuzumab deruxtecan is effective therapy in in vitro and in vivo preclinical models of NSCLC harboring ERBB2 amplification and report two cases of clinical activity of an anti-HER2 ADC in patients who acquired ERBB2 amplification after previous targeted therapy.
conclusionsHigh-level ERBB2 amplification reliably predicts HER2 overexpression in patients with NSCLC, and HER2 ADC is effective therapy in this population.
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