ArticleCancer science2018
Therapeutic strategies for afatinib-resistant lung cancer harboring HER2 alterations.
Article in Cancer science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- A three-gene signature correlated with MAPK/ERK activation characterizes acquired resistance to EGFR-tyrosine kinase inhibitors in non-small cell lung cancer.Oncology letters · 2026Article
- HER2 Alterations in Squamous Cell Lung Cancer: Biology, Therapeutic Landscape, and Emerging Precision Approaches.Cancers · 2026Review
- Oligoprogression in NSCLC with Other Actionable Oncogenic Drivers Beyond EGFR and ALK: An Emerging Entity.International journal of molecular sciences · 2026Review
- Novel Resistance Mechanisms to Second-Generation EGFR Tyrosine Kinase Inhibitor Afatinib and Associations With Genomic Features in NSCLC.Genes, chromosomes & cancer · 2025Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling.Nature communications · 2024Article
- SOS2 modulates the threshold of EGFR signaling to regulate osimertinib efficacy and resistance in lung adenocarcinoma.Molecular oncology · 2024Article
- SOS1 and KSR1 modulate MEK inhibitor responsiveness to target resistant cell populations based on PI3K and KRAS mutation status.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Overcoming MET-mediated resistance in oncogene-driven NSCLC.iScience · 2023Article
- SOS2 regulates the threshold of mutantbioRxiv : the preprint server for biology · 2023Article
- HER3 PET Imaging Predicts Response to Pan Receptor Tyrosine Kinase Inhibition Therapy in Gastric Cancer.Molecular imaging and biology · 2023Article
- Overcoming resistance to targeted therapy using MET inhibitors in solid cancers: evidence from preclinical and clinical studies.Medical oncology (Northwood, London, England) · 2021Review
- Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment.Journal of hematology & oncology · 2020Review
- Dissecting the mThe pharmacogenomics journal · 2020Article
- YES1 activation induces acquired resistance to neratinib in HER2-amplified breast and lung cancers.Cancer science · 2020Article
- Combining ERBB family and MET inhibitors is an effective therapeutic strategy in cutaneous malignant melanoma independent of BRAF/NRAS mutation status.Cell death & disease · 2019Article
- Acquired resistance mechanisms to afatinib in HER2-amplified gastric cancer cells.Cancer science · 2019Article
- Review
- Advances in Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer Based on Accurate Molecular Typing.Frontiers in pharmacology · 2019Review
- MET as resistance factor for afatinib therapy and motility driver in gastric cancer cells.PloS one · 2019Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human epidermal growth factor receptor 2 (HER2) plays an important role in the pathogenesis of various cancers. HER2 alterations have been suggested to be a therapeutic target in non-small-cell lung cancer (NSCLC), just as in breast and gastric cancers. We previously reported that the pan-HER inhibitor afatinib could be a useful therapeutic agent as HER2-targeted therapy for patients with NSCLC harboring HER2 alterations. However, acquired resistance to afatinib was observed in the clinical setting, similar to the case for other HER inhibitors. Thus, elucidation of the mechanisms underlying the development of acquired drug resistance and exploring means to overcome acquired drug resistance are important issues in the treatment of NSCLC. In this study, we experimentally established afatinib-resistant cell lines from NSCLC cell lines harboring HER2 alterations, and investigated the mechanisms underlying the acquisition of drug resistance. The established cell lines showed several unique afatinib-resistance mechanisms, including MET amplification, loss of HER2 amplification and gene expression, epithelial-to-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like features. The afatinib-resistant cell lines showing MET amplification were sensitive to the combination of afatinib plus crizotinib (a MET inhibitor), both in vitro and in vivo. The resistant cell lines which showed EMT or had acquired CSC-like features remained sensitive to docetaxel, like the parental cells. These findings may provide clues to countering the resistance to afatinib in NSCLC patients with HER2 alterations.
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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.