ArticleCells2020
Efficacy of the CDK7 Inhibitor on EMT-Associated Resistance to 3rd Generation EGFR-TKIs in Non-Small Cell Lung Cancer Cell Lines.
Article in Cells, 2020. 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, 23 citations in OpenAlex.
- PSMB1 screened by CRISPR-CAS9 promoted breast cancer progression via PI3K-AKT-mTOR signaling.Discover oncology · 2026Article
- Tumor Exosomal L1 Cell Adhesion Molecule Promotes Brain Metastasis of Lung Cancer.Research (Washington, D.C.) · 2026Article
- Targeting Transcriptional Cyclin-Dependent Kinases in Cancer.Molecular cancer therapeutics · 2025Review
- Potential Utility of a 4th-Generation EGFR-TKI and Exploration of Resistance Mechanisms-An In Vitro Study.Biomedicines · 2024Article
- Safety and efficacy of SNK01 (autologous natural killer cells) in combination with cytotoxic chemotherapy and/or cetuximab after failure of prior tyrosine kinase inhibitor in non-small cell lung cancer: non-clinical mouse model and phase I/IIa clinical study.Journal for immunotherapy of cancer · 2024Article
- The Resistance to EGFR-TKIs in Non-Small Cell Lung Cancer: From Molecular Mechanisms to Clinical Application of New Therapeutic Strategies.Pharmaceutics · 2023Review
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- GW4869 Can Inhibit Epithelial-Mesenchymal Transition and Extracellular HSP90α in Gefitinib-Sensitive NSCLC Cells.OncoTargets and therapy · 2023Article
- Tumor-associated macrophages mediate resistance of EGFR-TKIs in non-small cell lung cancer: mechanisms and prospects.Frontiers in immunology · 2023Review
- Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance.Journal of hematology & oncology · 2022Review
- THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours.Cell communication and signaling : CCS · 2022Article
- Blocking CDK7-Mediated NOTCH1-cMYC Signaling Attenuates Cancer Stem Cell Activity in Anaplastic Thyroid Cancer.Thyroid : official journal of the American Thyroid Association · 2022Article
- The Therapeutic Potential of the Restoration of the p53 Protein Family Members in theInternational journal of molecular sciences · 2022Review
- CDK7 is a prognostic biomarker for non-small cell lung cancer.Frontiers in oncology · 2022Article
- Contribution of p53 in sensitivity to EGFR tyrosine kinase inhibitors in non-small cell lung cancer.Scientific reports · 2021Article
- Inhibitors Targeting CDK9 Show High Efficacy against Osimertinib and AMG510 Resistant Lung Adenocarcinoma Cells.Cancers · 2021Article
- New strategy for suppressing the growth of lung cancer cells harboring mutations in the ATP-binding region of EGFR by targeting the molecular motor MYO1D.Clinical and translational medicine · 2021Article
- Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial to mesenchymal transition (EMT) is associated with resistance during EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy. Here, we investigated whether EMT is associated with acquired resistance to 3rd generation EGFR-TKIs, and we explored the effects of cyclin-dependent kinase 7 (CDK7) inhibitors on EMT-mediated EGFR-TKIs resistance in non-small cell lung cancer (NSCLC). We established 3rd generation EGFR-TKI resistant cell lines (H1975/WR and H1975/OR) via repeated exposure to WZ4002 and osimertinib. The two resistant cell lines showed phenotypic changes to a spindle-cell shape, had a reduction of epithelial marker proteins, an induction of vimentin expression, and enhanced cellular mobility. The EMT-related resistant cells had higher sensitivity to THZ1 than the parental cells, although THZ1 treatment did not inhibit EGFR activity. This phenomenon was also observed in TGF-β1 induced EMT cell lines. THZ1 treatment induced G2/M cell cycle arrest and apoptosis in all of the cell lines. In addition, THZ1 treatment led to drug-tolerant, EMT-related resistant cells, and these THZ1-tolerant cells partially recovered their sensitivity to 3rd generation EGFR-TKIs. Taken together, EMT was associated with acquired resistance to 3rd generation EGFR-TKIs, and CDK7 inhibitors could potentially be used as a therapeutic strategy to overcome EMT associated EGFR-TKI resistance in NSCLC.
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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.