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- Title
Natural Product-Based Glycolysis Inhibitors as a Therapeutic Strategy for Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer.
- Authors
Park, Wonyoung; Han, Jung Ho; Wei, Shibo; Yang, Eun-Sun; Cheon, Se-Yun; Bae, Sung-Jin; Ryu, Dongryeol; Chung, Hwan-Suck; Ha, Ki-Tae
- Abstract
Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. Targeted therapy against the epidermal growth factor receptor (EGFR) is a promising treatment approach for NSCLC. However, resistance to EGFR tyrosine kinase inhibitors (TKIs) remains a major challenge in its clinical management. EGFR mutation elevates the expression of hypoxia-inducible factor-1 alpha to upregulate the production of glycolytic enzymes, increasing glycolysis and tumor resistance. The inhibition of glycolysis can be a potential strategy for overcoming EGFR-TKI resistance and enhancing the effectiveness of EGFR-TKIs. In this review, we specifically explored the effectiveness of pyruvate dehydrogenase kinase inhibitors and lactate dehydrogenase A inhibitors in combating EGFR-TKI resistance. The aim was to summarize the effects of these natural products in preclinical NSCLC models to provide a comprehensive understanding of the potential therapeutic effects. The study findings suggest that natural products can be promising inhibitors of glycolytic enzymes for the treatment of EGFR-TKI-resistant NSCLC. Further investigations through preclinical and clinical studies are required to validate the efficacy of natural product-based glycolytic inhibitors as innovative therapeutic modalities for NSCLC.
- Subjects
EPIDERMAL growth factor receptors; NON-small-cell lung carcinoma; EPIDERMAL growth factor; PROTEIN-tyrosine kinases; PYRUVATE dehydrogenase kinase; GLYCOLYSIS; PROTEIN-tyrosine kinase inhibitors
- Publication
International Journal of Molecular Sciences, 2024, Vol 25, Issue 2, p807
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms25020807