Natural Product-Based Glycolysis Inhibitors as a Therapeutic Strategy for Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer
- Resource Type
- article
- Authors
- Wonyoung Park; Jung Ho Han; Shibo Wei; Eun-Sun Yang; Se-Yun Cheon; Sung-Jin Bae; Dongryeol Ryu; Hwan-Suck Chung; Ki-Tae Ha
- Source
- International Journal of Molecular Sciences, Vol 25, Iss 2, p 807 (2024)
- Subject
- natural products
NSCLC
EGFR-TKI
glycolysis inhibitor
PDK
LDHA
Biology (General)
QH301-705.5
Chemistry
QD1-999
- Language
- English
- ISSN
- 1422-0067
1661-6596
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.