ArticleCell cycle (Georgetown, Tex.)2015
Receptor tyrosine kinase ERBB4 mediates acquired resistance to ERBB2 inhibitors in breast cancer cells.
Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
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- Afatinib alone and in combination with vinorelbine or paclitaxel, in patients with HER2-positive breast cancer who failed or progressed on prior trastuzumab and/or lapatinib (LUX-Breast 2): an open-label, multicenter, phase II trial.Breast cancer research and treatment · 2022Trial
- Recurrent cancer-associated ERBB4 mutations are transforming and confer resistance to targeted therapies.Molecular oncology · 2026Article
- The role of genetics and epigenetics in breast cancer: A comprehensive review of metastasis, risk factors, and future perspectives.Journal of pharmaceutical analysis · 2025Review
- Article
- Multiple ligands simultaneous molecular docking and dynamics approach to study the synergetic inhibitory of curcumin analogs on ErbB4 tyrosine phosphorylation.Research in pharmaceutical sciences · 2024Article
- The Evolving Paradigm of Antibody-Drug Conjugates Targeting the ErbB/HER Family of Receptor Tyrosine Kinases.Pharmaceutics · 2024Review
- Deep (phospho)proteomics profiling of pre- treatment needle biopsies identifies signatures of treatment resistance in HER2Cell reports. Medicine · 2023Article
- MAVEN: compound mechanism of action analysis and visualisation using transcriptomics and compound structure data in R/Shiny.BMC bioinformatics · 2023Article
- Neuropilin-1 Knockout and Rescue Confirms Its Role to Promote Metastasis in MDA-MB-231 Breast Cancer Cells.International journal of molecular sciences · 2023Article
- Exploring potential molecular resistance and clonal evolution in advanced HER2-positive gastric cancer under trastuzumab therapy.Oncogenesis · 2023Article
- Challenges and future of HER2-positive gastric cancer therapy.Frontiers in oncology · 2023Review
- An overview of resistance to Human epidermal growth factor receptor 2 (Her2) targeted therapies in breast cancer.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Neratinib plus trastuzumab is superior to pertuzumab plus trastuzumab in HER2-positive breast cancer xenograft models.NPJ breast cancer · 2021Article
- Tyrosine Kinase Inhibitors Are Promising Therapeutic Tools for Cats with HER2-Positive Mammary Carcinoma.Pharmaceutics · 2021Article
- Nuclear factor erythroid 2-related factor 2 modulates HER4 receptor in ovarian cancer cells to influence their sensitivity to tyrosine kinase inhibitors.Exploration of targeted anti-tumor therapy · 2021Article
- Targeting the Notch Signaling Pathway in Chronic Inflammatory Diseases.Frontiers in immunology · 2021Review
- A newERJ open research · 2021Article
- Targeting the Human Epidermal Growth Factor Receptor Family in Breast Cancer beyond HER2.Breast care (Basel, Switzerland) · 2020Review
- Article
Corrections and comments
- Commented on by
- Erratum issuedErratum.2015
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Approximately 25% of breast cancers overexpress and depend on the receptor tyrosine kinase ERBB2, one of 4 ERBB family members. Targeted therapies directed against ERBB2 have been developed and used clinically, but many patients continue to develop resistance to such therapies. Although much effort has been focused on elucidating the mechanisms of acquired resistance to ERBB2-targeted therapies, the involvement of ERBB4 remains elusive and controversial. We demonstrate that genetic ablation of ERBB4, but not ERBB1-3, led to apoptosis in lapatinib-resistant cells, suggesting that the efficacy of pan-ERBB inhibitors was, at least in part, mediated by the inhibition of ERBB4. Moreover, ERBB4 was upregulated at the protein level in ERBB2+ breast cancer cell lines selected for acquired lapatinib resistance in vitro and in MMTV-Neu mice following prolonged lapatinib treatment. Knockdown of ERBB4 caused a decrease in AKT phosphorylation in resistant cells but not in sensitive cells, suggesting that ERBB4 activated the PI3K/AKT pathway in lapatinib-resistant cells. Importantly, ERBB4 knockdown triggered apoptosis not only in lapatinib-resistant cells but also in trastuzumab-resistant cells. Our results suggest that although ERBB4 is dispensable for naïve ERBB2+ breast cancer cells, it may play a key role in the survival of ERBB2+ cancer cells after they develop resistance to ERBB2 inhibitors, lapatinib and trastuzumab.
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