Circadian rhythm disruption and endocrine-related tumors

Abstract

This review delved into the intricate relationship between circadian clocks and physiological processes, emphasizing their critical role in maintaining homeostasis. Orchestrated by interlocked clock genes, the circadian timekeeping system regulates fundamental processes like the sleep-wake cycle, energy metabolism, immune function, and cell proliferation. The central oscillator in the hypothalamic suprachiasmatic nucleus synchronizes with light-dark cycles, while peripheral tissue clocks are influenced by cues such as feeding times. Circadian disruption, linked to modern lifestyle factors like night shift work, correlates with adverse health outcomes, including metabolic syndrome, cardiovascular diseases, infections, and cancer. We explored the molecular mechanisms of circadian clock genes and their impact on metabolic disorders and cancer pathogenesis. Specific associations between circadian disruption and endocrine tumors, spanning breast, ovarian, testicular, prostate, thyroid, pituitary, and adrenal gland cancers, are highlighted. Shift work is associated with increased breast cancer risk, with PER genes influencing tumor progression and drug resistance. CLOCK gene expression correlates with cisplatin resistance in ovarian cancer, while factors like aging and intermittent fasting affect prostate cancer. Our review underscored the intricate interplay between circadian rhythms and cancer, involving the regulation of the cell cycle, DNA repair, metabolism, immune function, and the tumor microenvironment. We advocated for integrating biological timing into clinical considerations for personalized healthcare, proposing that understanding these connections could lead to novel therapeutic approaches. Evidence supports circadian rhythm-focused therapies, particularly chronotherapy, for treating endocrine tumors. Our review called for further research to uncover detailed connections between circadian clocks and cancer, providing essential insights for targeted treatments. We emphasized the importance of public health interventions to mitigate lifestyle-related circadian disruptions and underscored the critical role of circadian rhythms in disease mechanisms and therapeutic interventions.

Keywords: Circadian rhythm; Circadian disruption; Shift work; CLOCK gene; Cancer; Endocrine tumors; Chronotherapy

Core Tip: This review explored the pivotal role of circadian clocks in physiological processes and adverse health outcomes, including metabolic syndrome and cancer, linked to their disruption. Orchestrated by interlocked CLOCK genes, the circadian system regulates vital functions, from sleep-wake cycles to immune response. Disruptions, often from night shift work, correlate with increased risks, notably in endocrine tumors. Molecular insights highlight potential therapeutic vistas, emphasizing the need for integrating circadian considerations in personalized healthcare. Chronotherapy emerges as a promising approach for endocrine tumor treatment, urging further research into precise mechanisms and public health interventions to mitigate lifestyle-related circadian disruptions.