ArticleCancer science2020
Glycogen synthase kinase-3 inhibition overcomes epithelial-mesenchymal transition-associated resistance to osimertinib in EGFR-mutant lung cancer.
Article in Cancer science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Harnessing GSK-3β inhibition for lung cancer therapy: emerging opportunities and challenges.Medical oncology (Northwood, London, England) · 2025Review
- Epigenetic potentiation of 5-fluorouracil by HDAC inhibitor quisinostat enhances antitumor effects in colorectal cancer.Cancer cell international · 2025Article
- Transcriptomic-Driven Drug Repurposing Reveals SP600125 as a Promising Drug Candidate for the Treatment of Glial-Mesenchymal Transition in Glioblastoma.International journal of molecular sciences · 2025Article
- Targeting WEE1 to Overcome ARID1A Mutation-Driven Osimertinib Resistance in EGFR-Mutant Lung Cancer.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025Article
- Drug tolerance and persistence to EGFR inhibitor treatment are mediated by an ILK-SFK-YAP signaling axis in lung adenocarcinoma.Oncogene · 2025Article
- EGFR mutations in non-small cell lung cancer: Classification, characteristics and resistance to third-generation EGFR-tyrosine kinase inhibitors (Review).Oncology letters · 2025Review
- 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
- The changing treatment landscape of EGFR-mutant non-small-cell lung cancer.Nature reviews. Clinical oncology · 2025Review
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- Targeting non-coding RNAs to overcome osimertinib resistance inFrontiers in oncology · 2024Review
- Composition of Conditioned Media from Radioresistant and Chemoresistant Cancer Cells Reveals miRNA and Other Secretory Factors Implicated in the Development of Resistance.International journal of molecular sciences · 2023Review
- Biphasic function of GSK3β in gefitinib‑resistant NSCLC with or without EGFR mutations.Experimental and therapeutic medicine · 2023Article
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- GSK3 inhibition circumvents and overcomes acquired lorlatinib resistance in ALK-rearranged non-small-cell lung cancer.NPJ precision oncology · 2022Article
- 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
- Review
- Trametinib overcomes KRAS-G12V-induced osimertinib resistance in a leptomeningeal carcinomatosis model of EGFR-mutant lung cancer.Cancer science · 2021Article
- Review
- Glycogen synthase kinase-3 inhibition overcomes epithelial-mesenchymal transition-associated resistance to osimertinib in EGFR-mutant lung cancer.Cancer science · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, osimertinib, has marked efficacy in patients with EGFR-mutant lung cancer. While epithelial-mesenchymal transition (EMT) plays a role in the resistance to various targeted drugs, its involvement in EGFR-inhibitor resistance remains largely unknown. Preclinical experiments with osimertinib-resistant lung cancer cells showed that EMT was associated with decreased microRNA-200c and increased ZEB1 expression. In several resistant clone cells, pretreatment with the histone deacetylase inhibitor quisinostat helped overcome the resistance by reverting EMT. Furthermore, drug screening from a library of 100 kinase inhibitors indicated that Glycogen synthase kinase-3 (GSK-3) inhibitors, such as LY2090314, markedly inhibited the growth and induced apoptosis of resistant cells, specifically those with a mesenchymal phenotype. These results suggest that GSK-3 inhibition could be useful to circumvent EMT-associated resistance to osimertinib in EGFR-mutant lung cancer.
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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.