Disruption of cellular timekeeping in cancer: links between circadian clocks, metabolism, and tumor progression.

Disruption of cellular timekeeping systems is a key driver of cancer cell development and progression. The circadian clock is a 24-hour regulatory system that relies on core clock genes - CLOCK, BMAL1, PER, and CRY. Maintaining cellular homeostasis is essential, as it regulates processes such as the cell cycle, metabolism, DNA repair, and apoptosis. Disruption of Circadian rhythms is common in cancer, altering gene expression and causing the mis-timing of cellular events. This disturbance stimulates excessive growth, genetic instability, and resistance to cell death. Circadian rhythms and tumour growth disruption are linked by metabolic reprogramming. Cancer cells show enhanced glycolysis, lipid production, and modified mitochondrial activity, all of which are typically regulated by the circadian clock. The irregular functioning of clock genes leads to metabolic changes that facilitate tumor development and survival. This also enhances metastatic progression by regulating the tumor's angiogenesis, inflammation, and immunological responses. Recent studies posit the clinical relevance of targeting circadian circuits in cancer therapy. Chronotherapy is the practice of administering therapies in accordance with the body's biological rhythms. It is expected to increase the treatment's therapeutic efficacy while decreasing toxicity significantly. This review underscores the complex molecular connections between circadian clock disruption, metabolic changes, and tumor progression. It highlights the potential of incorporating circadian biology into cancer research to advance biomarker discovery, precision oncology, and the creation of novel therapeutic strategies.