Circadian Clock Genes in Colorectal Cancer: From Molecular Mechanisms to Chronotherapeutic Applications

Colorectal cancer (CRC) is a life-threatening malignancy, but our understanding of its pathogenic mechanisms remains incomplete—posing a major constraint on the development of effective therapeutic strategies. The transcription-translation feedback loop of clock genes (e.g., BMAL1, CLOCK, PER1/2/3, and CRY1/2) provides a promising novel avenue for deciphering the initiation and progression of CRC. Mounting evidence indicates that core circadian clock genes play pivotal roles in CRC oncogenesis by orchestrating the regulation of the cell cycle, epithelial–mesenchymal transition (EMT), metabolic reprogramming, and the tumor microenvironment. This review systematically summarizes the expression patterns and mechanistic roles of core clock genes in CRC, while elucidating their molecular underpinnings in tumor progression via key signaling cascades (e.g., Wnt/β-catenin and c-Myc/p21 pathways). We emphasize the associations between circadian disruption and CRC—including diagnostic markers, prognostic assessment, and chemosensitivity—and provide an in-depth discussion of chronotherapeutic strategies and their translational potential. Finally, we identify unaddressed scientific questions and propose future research directions to facilitate the development of novel targeted therapies for CRC.