Circadian clock control of breast cancer hallmarks: molecular mechanisms and therapeutic implications

Circadian rhythms regulate physiological functions and critical biological processes in almost all living forms. The circadian system enables organisms to anticipate and adapt to environmental fluctuations, thereby optimizing physiological responses. Proper synchronization between the master pacemaker in the brain and peripheral clocks throughout the organism is essential for maintaining homeostasis and promoting health. Conversely, circadian misalignment is increasingly recognized as a contributing factor in the pathogenesis of various diseases. Emerging evidence implicates circadian disruption as a driver of carcinogenesis. Indeed, epidemiological studies have associated night-shift work and chronic jet lag with an increased risk of cancer. At the molecular level, the biological clock comprises a complex network of transcriptional-translational feedback loops that generates approximately 24-h cycles in gene expression across all tissues. Notably, many clock-regulated genes participate in key pathways relevant to tumorigenesis, including cell cycle regulation, DNA damage repair, angiogenesis, and metabolism. Moreover, the circadian clock represents a promising therapeutic target in oncology. Numerous clinical trials have demonstrated that chronomodulation of chemotherapeutic agents can enhance treatment efficacy while mitigating adverse effects, thereby improving the quality of life for cancer patients. Hence, advancing our understanding of the molecular interplay between circadian regulation and cancer development may elucidate the role of circadian rhythms in tumorigenesis, facilitate the identification of novel prognostic markers and therapeutic targets, and ultimately improve outcomes in breast cancer patients.