ArticleCancer2020
Overcoming acquired resistance of epidermal growth factor receptor-mutant non-small cell lung cancer cells to osimertinib by combining osimertinib with the histone deacetylase inhibitor panobinostat (LBH589).
Article in Cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Osimertinib-induced cardiotoxicity is driven by HDAC-dependent epigenetic repression and rescued by vorinostat.Signal transduction and targeted therapy · 2026Article
- FAM72A is associated with lung cancer proliferation and migration via the NF‑κB signaling pathway.Molecular genetics and genomics : MGG · 2026Article
- Challenges in Diagnosis of Lepidic Subtype in Lung Cancer According to W.H.O Classification: A Case Report.British journal of biomedical science · 2026Article
- Astatine-211-Labeled Therapy Targeting Amino Acid Transporters: Overcoming Drug Resistance in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2025Review
- Panobinostat potentiates adagrasib-induced cell death by triggering autophagy in human non-small cell lung cancer.Cell death discovery · 2025Article
- Epithelial-mesenchymal transition (EMT) and its role in acquired epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) chemoresistance in non-small cell lung cancer (NSCLC).Cancer pathogenesis and therapy · 2025Review
- HDAC1 and FOXK1 mediate EGFR-TKI resistance of non-small cell lung cancer through miR-33a silencing.Journal of translational medicine · 2024Article
- Review
- Targeting the SMURF2-HIF1α axis: a new frontier in cancer therapy.Frontiers in oncology · 2024Review
- Genetic alterations predict poor efficacy, outcomes and resistance to second-line osimertinib treatment in non-small cell lung cancer.American journal of cancer research · 2024Article
- Circumvention of Gefitinib Resistance by Repurposing Flunarizine via Histone Deacetylase Inhibition.ACS pharmacology & translational science · 2023Article
- Repurposing of triamterene as a histone deacetylase inhibitor to overcome cisplatin resistance in lung cancer treatment.Journal of cancer research and clinical oncology · 2023Article
- Histone modifications in drug-resistant cancers: From a cancer stem cell and immune evasion perspective.Experimental & molecular medicine · 2023Review
- Hypoxia-Inducible Factor-1: A Novel Therapeutic Target for the Management of Cancer, Drug Resistance, and Cancer-Related Pain.Cancers · 2022Review
- Targeting apoptosis to manage acquired resistance to third generation EGFR inhibitors.Frontiers of medicine · 2022Review
- Preclinical Models for Acquired Resistance to Third-Generation EGFR Inhibitors in NSCLC: Functional Studies and Drug Combinations Used to Overcome Resistance.Frontiers in oncology · 2022Review
- Targeting Ferroptosis Pathway to Combat Therapy Resistance and Metastasis of Cancer.Frontiers in pharmacology · 2022Review
- [Research Progress of Epigenetic Mechanism in Acquired Resistance of Targeted Therapy in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Review
- Targeting c-Myc to Overcome Acquired Resistance of EGFR Mutant NSCLC Cells to the Third-Generation EGFR Tyrosine Kinase Inhibitor, Osimertinib.Cancer research · 2021Article
- Nanoparticles for co-delivery of osimertinib and selumetinib to overcome osimertinib-acquired resistance in non-small cell lung cancer.Acta biomaterialia · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe major clinical obstacle that limits the long-term benefits of treatment with osimertinib (AZD9291) in patients with epidermal growth factor receptor-mutant non-small cell lung cancer is the development of acquired resistance. Therefore, effective strategies that can overcome acquired resistance to osimertinib are urgently needed. The authors' current efforts in this direction have identified LBH589 (panobinostat), a clinically used histone deacetylase inhibitor, as a potential agent in overcoming osimertinib resistance.
methodsCell growth and apoptosis in vitro were evaluated by measuring cell numbers and colony formation and by detecting annexin V-positive cells and protein cleavage, respectively. Drug effects on tumor growth in vivo were assessed with xenografts in nude mice. Alterations of tested proteins in cells were monitored with Western blot analysis. Gene knockout was achieved using the CRISPR/Cas9 technique.
resultsThe combination of LBH589 and osimertinib synergistically decreased the survival of different osimertinib-resistant cell lines, including those harboring C797S mutations, with greater inhibition of cell colony formation and growth. The combination enhanced the induction of apoptosis in osimertinib-resistant cells. Importantly, the combination effectively inhibited the growth of osimertinib-resistant xenograft tumors in nude mice. Mechanistically, the combination of LBH589 and osimertinib enhanced the elevation of Bim in osimertinib-resistant cells. Knockout of Bim in osimertinib-resistant cells substantially attenuated or abolished apoptosis enhanced by the LBH589 and osimertinib combination. These results collectively support a critical role of Bim elevation in the induction of apoptosis of osimertinib-resistant cells for this combination.
conclusionsThe current findings provide strong preclinical evidence in support of the potential for LBH589 to overcome osimertinib resistance in the clinic.
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