ArticleMolecular oncology2015
HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer.
Article in Molecular oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.Nature medicine · 2025Trial
- Neratinib Efficacy and Circulating Tumor DNA Detection ofClinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- High-throughput characterization of 5886 HER2 variants identifies 112 new in cellulo gain-of-function mutations.Genomics · 2025Article
- New Gain-of-Function Mutations Prioritize Mechanisms of HER2 Activation.medRxiv : the preprint server for health sciences · 2025Article
- HER2-Positive Breast Cancer Treatment and Resistance.Advances in experimental medicine and biology · 2025Review
- TMB is associated with the prognosis of egfr-mutated non-small cell lung cancer in Xuanwei, China.Biomarkers in medicine · 2024Article
- Tailoring Neoadjuvant Therapy in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Recent Advances and Strategies.JCO oncology practice · 2024Review
- Clinical value of next-generation sequencing in guiding decisions regarding endocrine therapy for advanced HR-positive/HER-2-negative breast cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2022Article
- Association between genome-wide epigenetic and genetic alterations in breast cancer tissue and response to HER2-targeted therapies in HER2-positive breast cancer patients: new findings and a systematic review.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Cross-Resistance Among Sequential Cancer Therapeutics: An Emerging Issue.Frontiers in oncology · 2022Review
- Review
- Towards personalized treatment for early stage HER2-positive breast cancer.Nature reviews. Clinical oncology · 2020Review
- Molecular landscape and efficacy of HER2-targeted therapy in patients with HER2-mutated metastatic breast cancer.NPJ breast cancer · 2020Article
- Defining the landscape of ATP-competitive inhibitor resistance residues in protein kinases.Nature structural & molecular biology · 2020Article
- Identification of an eight-lncRNA prognostic model for breast cancer using WGCNA network analysis and a Cox‑proportional hazards model based on L1-penalized estimation.International journal of molecular medicine · 2019Article
- Neratinib is effective in breast tumors bearing both amplification and mutation of ERBB2 (HER2).Science signaling · 2018Article
- Frequency, impact and a preclinical study of novelTherapeutic advances in medical oncology · 2018Article
- Review
- HER2 Reactivation through Acquisition of the HER2 L755S Mutation as a Mechanism of Acquired Resistance to HER2-targeted Therapy in HER2Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- De-escalation of treatment in HER2-positive breast cancer: Determinants of response and mechanisms of resistance.Breast (Edinburgh, Scotland) · 2017Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 4 countries.
Funding
Abstract
Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. Understanding the molecular pathways that contribute to the development of drug resistance is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER family mutations in breast cancer. Because mutations within HER1/EGFR are predictive of response to tyrosine kinase inhibitors (TKI) in lung cancer, we investigated whether mutations in HER family kinase domains are predictive of response to targeted therapy in HER2-overexpressing breast cancer. We sequenced the HER family kinase domains from 76 HER2-overexpressing invasive carcinomas and identified 12 missense variants. Patients whose tumors carried any of these mutations did not respond to HER2 directed therapy in the metastatic setting. We developed mutant cell lines and used structural analyses to determine whether changes in protein conformation could explain the lack of response to therapy. We also functionally studied all HER2 mutants and showed that they conferred an aggressive phenotype and altered effects of the TKI lapatinib. Our data demonstrate that mutations in the finely tuned HER kinase domains play a critical function in breast cancer progression and may serve as prognostic and predictive markers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.