When Clocks Go Rogue: Circadian Rhythms and the Rise of Cancer

This review summarizes recent insights into the roles of the circadian clock in regulating cancer hallmarks, with a focus on its impact on the tumor microenvironment, and highlights the translational promise of circadian-informed strategies for cancer therapy. The circadian clock is a 24-hour biological timekeeping system that aligns physiological processes with cyclic environmental cues, such as light-dark cycles. Disruptions of circadian rhythms caused by lifestyle factors, including shift work, irregular sleep patterns, and jet lag, can lead to physiological dysregulation and increased risk of various diseases including cancer, positioning the circadian clock as both a critical driver of tumorigenesis and a potential target for chronotherapies. This review provides a comprehensive overview of circadian regulation in tumorigenesis across diverse cancer types by framing its role according to established cancer hallmarks, with particular emphasis on how the circadian system shapes immune cell dynamics within the tumor microenvironment to modulate tumor progression and immune surveillance. We further discuss recent preclinical and clinical advances in chronotherapy, highlighting how aligning therapeutic interventions with biological rhythms can enhance treatment efficacy, including responses to immunotherapy. By integrating mechanistic insights with translational applications, this review bridges circadian biology and oncology, providing a framework for future chronobiology-based cancer therapies.