ArticleExperimental & molecular medicine2024
Targeting pyruvate dehydrogenase kinase 1 overcomes EGFR C797S mutation-driven osimertinib resistance in non-small cell lung cancer.
Article in Experimental & molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Thalamic PDK-PDHA1 Signaling is Associated with Opioid-Induced Loss-of-Righting-Reflex Sensitivity: Evidence from Phosphoproteomic Profiling and PDK Pathway Intervention.Neurochemical research · 2026Article
- Review
- Chemical Bond-Orchestrated Energy Depletion to Augment Lung Cancer Chemo-Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Leonurine suppresses renal cell carcinoma progression by targeting the PDK1-mediated Warburg effect.Translational andrology and urology · 2026Article
- Review
- Charting the blueprint: a bibliometric analysis reveals future strategies in lung cancer targeted therapy (2003-2025).Journal of thoracic disease · 2026Article
- Identification of a Prognostic Gene Signature for Chemoresistance Prediction in Lung Adenocarcinoma by Screening Mitochondrial Metabolism Gene Sets.International journal of molecular sciences · 2026Article
- USP5-mediated CD73 deubiquitination drives osimertinib resistance via PI3K/AKT and glycolysis activation in LUAD.iScience · 2026Article
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- Nano-Enabled Fluorescence Switching: A Novel Strategy for PDGFRβ Detection and TKI Therapy Monitoring.Research (Washington, D.C.) · 2026Article
- Drug resistance in cancer: molecular mechanisms and emerging treatment strategies.Molecular biomedicine · 2025Review
- Cancer-associated fibroblasts promote EGFR-TKI resistance via the CTHRC1/glycolysis/H3K18la positive feedback loop.Oncogene · 2025Article
- Strategies Beyond 3rd EGFR-TKI Acquired Resistance: Opportunities and Challenges.Cancer medicine · 2025Review
- MYST2 histone acetyltransferase promotes lung adenocarcinoma progression by regulating the p38 MAPK signaling pathway.Translational oncology · 2025Article
- Osimertinib acquired resistance among patients with EGFR-mutated NSCLC: from molecular mechanisms to clinical therapeutic strategies.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- A predictive model for anlotinib-osimertinib efficacy in advanced non-small cell lung cancer with acquired resistance: circulating tumor DNA and angiogenesis markers.American journal of translational research · 2025Article
- Harnessing glucose metabolism with nanomedicine for cancer treatment.Theranostics · 2024Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Osimertinib, a selective third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), effectively targets the EGFR T790M mutant in non-small cell lung cancer (NSCLC). However, the newly identified EGFR C797S mutation confers resistance to osimertinib. In this study, we explored the role of pyruvate dehydrogenase kinase 1 (PDK1) in osimertinib resistance. Patients exhibiting osimertinib resistance initially displayed elevated PDK1 expression. Osimertinib-resistant cell lines with the EGFR C797S mutation were established using A549, NCI-H292, PC-9, and NCI-H1975 NSCLC cells for both in vitro and in vivo investigations. These EGFR C797S mutant cells exhibited heightened phosphorylation of EGFR, leading to the activation of downstream oncogenic pathways. The EGFR C797S mutation appeared to increase PDK1-driven glycolysis through the EGFR/AKT/HIF-1α axis. Combining osimertinib with the PDK1 inhibitor leelamine helped successfully overcome osimertinib resistance in allograft models. CRISPR-mediated PDK1 knockout effectively inhibited tumor formation in xenograft models. Our study established a clear link between the EGFR C797S mutation and elevated PDK1 expression, opening new avenues for the discovery of targeted therapies and improving our understanding of the roles of EGFR mutations in cancer progression.
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