Haoya Wang Et Al.: Circadian Rhythm Disruption Promotes Tumor Progression Through Upregulated Glycolysis

Aberrant activation of glycolysis (Warburg effect) constitutes a key metabolic reprogramming feature in malignant tumors, serving as a critical mechanism facilitating tumor development. Within the tumor microenvironment, this glycolytic reprogramming emerges in diverse cellular components, including cancer cells, immune cells (e.g., myeloid-derived suppressor cells and tumor-associated macrophages), and fibroblasts, thereby establishing a microenvironment that promotes tumor invasion and metastasis. Recent studies have revealed that the endogenous circadian system orchestrates glycolysis processes through multiple pathways, where circadian rhythm disruption frequently manifests as upregulated glycolysis with pro-tumorigenic consequences.

This review summarizes the specific mechanisms through which circadian rhythm disruption regulates the reprogramming of glycolytic metabolism in the tumor microenvironment. Emerging chronotherapeutic strategies focus on targeting glycolytic pathways.

The reprogramming promotes enhanced glycolysis, ultimately accelerating tumor progression. Combination therapy with glycolysis inhibitors has the potential to further improve efficacy when optimized for time. Future research should prioritize unraveling the complex interplay between circadian rhythms, glycolysis, and the tumor microenvironment to advance more effective therapeutic interventions.