Circadian rhythm: An emerging force for colorectal cancer treatment

The relationship between circadian rhythm disorder and the occurrence and progression of colorectal cancer (CRC) has received attention. The circadian rhythm is maintained by the central clock located in the suprachiasmatic nucleus of the hypothalamus and peripheral oscillators throughout the body. The core clock genes, including CLOCK, BMAL1, PER, and CRY, regulate cell cycle, DNA repair, metabolic homeostasis, and immune surveillance through transcriptional translation feedback loops. In CRC, mutations or expression imbalances in clock genes lead to checkpoint inactivation, attenuated apoptosis, and genomic instability. These disruptions drive tumorigenesis and malignant progression by remodeling the tumor microenvironment (TME). Recent studies revealed circadian-dependent regulation of key oncogenic pathways (mTOR, MAPK/ERK, Wnt/β-catenin) and time-dependent oscillations in immune cell activity, angiogenesis, and metabolic patterns. In clinical practice, chronotherapy strategies based on circadian rhythms have demonstrated enhanced efficacy, radiation sensitivity, and immune responses in preclinical models, with clinical trials validating their potential to improve outcomes while reducing toxicity. In addition, clock gene expression profiles emerge as independent prognostic biomarkers for CRC. Future research needs to integrate multiple omics datasets, and artificial intelligence models can analyze the circadian regulation network in CRC, providing new ideas for the precise prevention and treatment of CRC.