Wang Haoya, Wu Di, Li Jie, Zhao Binghe, Liu Lu, Wang Xinxin
The First Medical Center of PLA General Hospital, Beijing, China.
Cancer Med. 2025 Aug;14(15):e71138. doi: 10.1002/cam4.71138.
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.
糖酵解异常激活（瓦伯格效应）是恶性肿瘤关键的代谢重编程特征，是促进肿瘤发展的关键机制。在肿瘤微环境中，这种糖酵解重编程出现在多种细胞成分中，包括癌细胞、免疫细胞（如髓源性抑制细胞和肿瘤相关巨噬细胞）和成纤维细胞，从而建立促进肿瘤侵袭和转移的微环境。最近的研究表明，内源性昼夜节律系统通过多种途径协调糖酵解过程，昼夜节律紊乱常表现为糖酵解上调并产生促肿瘤后果。
本综述总结了昼夜节律紊乱调节肿瘤微环境中糖酵解代谢重编程的具体机制。新兴的时辰治疗策略聚焦于靶向糖酵解途径。
这种重编程促进糖酵解增强，最终加速肿瘤进展。当针对时间进行优化时，糖酵解抑制剂联合治疗有可能进一步提高疗效。未来的研究应优先阐明昼夜节律、糖酵解和肿瘤微环境之间的复杂相互作用，以推进更有效的治疗干预措施。
