Circadian Rhythm and Carcinogenesis
Özet
The molecular circadian clock, composed of master regulators in the suprachiasmatic nucleus (SCN) and peripheral tissues, maintains a ~24-hour cycle of biochemical and physiological processes through autonomous transcription-translation feedback loops. Core positive elements (CLOCK and BMAL1) and negative feedback loops (PER, CRY, and REV-ERBs) regulate essential cellular operations. Disruptions in this internal timekeeping mechanism—induced by shift work, jet lag, and metabolic changes—are strongly linked to genomic instability and accelerated carcinogenesis. Healthy and cancerous tissues show significant differences in clock gene expression; specifically, variations in genes like Per1, Per2, and Bmal1 disrupt key cell cycle checkpoints (such as G1-S and G2-M transitions), DNA damage repair (DDR) pathways, and tumor suppression functions. Furthermore, the bidirectional link between the circadian rhythm and cellular metabolism alters vital adaptations like the Warburg effect and SIRT1-mediated apoptosis. Understanding these altered molecular rhythms introduces chronotherapy, which strategically coordinates the administration of chemotherapy, radiotherapy, or melatonin to maximize treatment efficacy while minimizing toxic side effects in normal cells. Ultimately, leveraging these rhythmic dynamics offers promising targets for developing novel prognostic markers and optimizing cancer therapeutics.
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