ArticleMolecular oncology2016
EMT is associated with, but does not drive resistance to ALK inhibitors among EML4-ALK non-small cell lung cancer.
Article in Molecular oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Chaperone directed heterobifunctional molecules circumvent KRASCancer letters · 2025Article
- Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.Journal of hematology & oncology · 2025Review
- Research progress on the role of bypass activation mechanisms in resistance to tyrosine kinase inhibitors in non-small cell lung cancer.Frontiers in oncology · 2024Review
- ALK inhibitors in cancer: mechanisms of resistance and therapeutic management strategies.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- From Development to Place in Therapy of Lorlatinib for the Treatment of ALK and ROS1 Rearranged Non-Small Cell Lung Cancer (NSCLC).Diagnostics (Basel, Switzerland) · 2023Review
- Overcoming MET-mediated resistance in oncogene-driven NSCLC.iScience · 2023Article
- Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future directions.Frontiers of medicine · 2023Review
- Silibinin Overcomes EMT-Driven Lung Cancer Resistance to New-Generation ALK Inhibitors.Cancers · 2022Article
- Alternative Treatment Options to ALK Inhibitor Monotherapy for EML4-ALK-Driven Lung Cancer.Cancers · 2022Review
- An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance.Bosnian journal of basic medical sciences · 2022Review
- Lung Cancer Management with Silibinin: A Historical and Translational Perspective.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Next-Generation Sequencing with Liquid Biopsies from Treatment-Naïve Non-Small Cell Lung Carcinoma Patients.Cancers · 2021Review
- Long non-coding RNAs in lung cancer: implications for lineage plasticity-mediated TKI resistance.Cellular and molecular life sciences : CMLS · 2021Review
- Review
- Acquired resistance to targeted therapies in NSCLC: Updates and evolving insights.Pharmacology & therapeutics · 2020Review
- Tumor evolution in epidermal growth factor receptor mutated non-small cell lung cancer.Journal of thoracic disease · 2020Review
- The role ofCancer cell international · 2019Review
- Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review.Oncotarget · 2018Article
- The function and therapeutic targeting of anaplastic lymphoma kinase (ALK) in non-small cell lung cancer (NSCLC).Molecular cancer · 2018Review
- Mutations in EMT-Related Genes in ALK Positive Crizotinib Resistant Non-Small Cell Lung Cancers.Cancers · 2018Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ALK gene fusion occurs in approximately 3-7% of non-small cell lung cancer (NSCLC). For patients with ALK positive NCSLC, crizotinib and ceritinib are FDA approved ALK inhibitors, however, patients inevitably acquire resistance to such therapies typically within one to two years. Interrogation of in vitro ALK-positive NSCLC cell line models of acquired resistance to first and second-generation ALK inhibitors revealed acquired epithelial-to-mesenchymal transition (EMT) mechanisms. Here we demonstrated that knockdown of upregulated mesenchymal markers in acquired resistant lines decreased the invasive and migratory capabilities of the cells, however, it did not restore sensitivity to ALK inhibitors. Removing drug for 5 weeks from H3122 cell line that acquired resistance to ceritinib restored its sensitivity to ceritinib. In addition, HSP90 inhibitors ganetespib and 17-AAG were potent in inducing cell death in cell lines resistant to crizotinib and ceritinib. Taken together, EMT does not drive resistance to ALK inhibitors and HSP90 inhibition demonstrates more efficacy when further ALK inhibition may not. This study warrants more exploration of HSP90 inhibitors for ALK-positive patients who progress on 1st and 2nd line ALK inhibitor therapy.
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