Targeting Glycolytic Metabolism in Cancer Therapy: Current Approaches and Future Perspectives

Area of Science:

• Oncology
• Metabolic pathways
• Cancer therapeutics

Background:

• The Warburg effect, or aerobic glycolysis, is a hallmark of cancer metabolism.
• Targeting this pathway offers a promising therapeutic strategy for cancer treatment.
• Key glycolysis components like GLUTs and enzymes (HK2, PFK, GAPDH, PKM2, LDHA) are crucial.

Purpose of the Study:

• To review regulatory mechanisms and therapeutic potential of glycolysis pathway components.
• To evaluate inhibitors, clinical landscape, and limitations of monotherapy.
• To explore synergistic interactions and future directions for glycolysis-targeted therapy.

Main Methods:

• Review of literature on glycolysis pathway components and their inhibitors.
• Analysis of molecular mechanisms of inhibitors and clinical development.
• Exploration of combination strategies with other cancer therapies.

Main Results:

• Monotherapy limitations arise from tumor metabolic plasticity and off-target toxicity in normal cells.
• Synergistic interactions observed between glycolysis inhibitors and chemotherapy, radiotherapy, immunotherapy, photothermal therapy, and targeted therapy.
• Rational combination strategies show potential to overcome resistance and enhance efficacy.

Conclusions:

• Achieving selective inhibition of cancer cell glycolysis while sparing normal cells is the primary challenge.
• Development of high-selectivity agents, cancer-specific nanodelivery, biomarkers, and metabolic-immune combination regimens are crucial.
• These advancements are vital for clinical translation of glycolysis-targeted cancer therapy.