Natural Product-Based Glycolysis Inhibitors as a Therapeutic Strategy for Epidermal Growth Factor Receptor-Tyrosine
Wonyoung Park1,2, Jung Ho Han3, Shibo Wei4
1Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
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.
Insights
Natural products show promise in inhibiting glycolysis to overcome resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). Further studies are needed to confirm their therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Non-small cell lung cancer (NSCLC) is a major global health concern.
- Epidermal growth factor receptor (EGFR) targeted therapy offers a promising treatment avenue for NSCLC.
- Resistance to EGFR tyrosine kinase inhibitors (TKIs) poses a significant clinical challenge.
Purpose of the Study:
- To review the potential of natural products as inhibitors of glycolytic enzymes.
- To explore their efficacy in overcoming EGFR-TKI resistance in NSCLC.
- To summarize findings from preclinical NSCLC models.
Main Methods:
- Review of existing literature on natural products targeting glycolysis.
- Focus on pyruvate dehydrogenase kinase (PDK) and lactate dehydrogenase A (LDHA) inhibitors.
- Analysis of preclinical NSCLC models evaluating EGFR-TKI resistance.
Main Results:
- EGFR mutations increase glycolysis via hypoxia-inducible factor-1 alpha, contributing to TKI resistance.
- Inhibiting glycolysis, particularly via PDK and LDHA, can enhance EGFR-TKI effectiveness.
- Natural products demonstrate potential as glycolytic inhibitors in preclinical settings.
Conclusions:
- Natural products targeting glycolytic enzymes represent a potential strategy against EGFR-TKI-resistant NSCLC.
- Further preclinical and clinical research is essential to validate these findings.
- Natural product-based glycolytic inhibitors could offer innovative therapeutic options for NSCLC.
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