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Circadian rhythms, intrinsic cycles spanning approximately 24 h, regulate numerous physiological processes, including sleep–wake cycles, hormone release, and metabolism. These rhythms are orchestrated by the circadian clock, primarily located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Disruptions in circadian rhythms, whether due to genetic mutations, environmental factors, or lifestyle choices, can significantly impact health, contributing to disorders such as sleep disturbances, metabolic syndrome, and cardiovascular diseases. Additionally, there is a profound link between the disruption of circadian rhythms and development of various cancer, the influence on disease incidence and progression. This incurred regulation by circadian clock on pathways has its implication in tumorigenesis, such as cell cycle control, DNA damage response, apoptosis, and metabolism. Furthermore, the circadian timing system modulates the efficacy and toxicity of cancer treatments. In cancer treatment, the use of chronotherapy to optimize the timing of medical treatments, involves administering chemotherapy, radiation, or other therapeutic interventions at specific intervals to enhance efficacy and minimize side effects. This approach capitalizes on the circadian variations in cellular processes, including DNA repair, cell cycle progression, and drug metabolism. Preclinical and clinical studies have demonstrated that chronotherapy can significantly improve the therapeutic index of chemotherapeutic agents like cisplatin and 5-fluorouracil by enhancing anticancer activity and reducing toxicity. Further research is needed to elucidate the mechanisms underlying circadian regulation of cancer and to develop robust chronotherapeutic protocols tailored to individual patients’ circadian profiles, potentially transforming cancer care into more effective and personalized treatment strategies.
Circadian rhythms, intrinsic cycles spanning approximately 24 h, regulate numerous physiological processes, including sleep–wake cycles, hormone release, and metabolism. These rhythms are orchestrated by the circadian clock, primarily located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Disruptions in circadian rhythms, whether due to genetic mutations, environmental factors, or lifestyle choices, can significantly impact health, contributing to disorders such as sleep disturbances, metabolic syndrome, and cardiovascular diseases. Additionally, there is a profound link between the disruption of circadian rhythms and development of various cancer, the influence on disease incidence and progression. This incurred regulation by circadian clock on pathways has its implication in tumorigenesis, such as cell cycle control, DNA damage response, apoptosis, and metabolism. Furthermore, the circadian timing system modulates the efficacy and toxicity of cancer treatments. In cancer treatment, the use of chronotherapy to optimize the timing of medical treatments, involves administering chemotherapy, radiation, or other therapeutic interventions at specific intervals to enhance efficacy and minimize side effects. This approach capitalizes on the circadian variations in cellular processes, including DNA repair, cell cycle progression, and drug metabolism. Preclinical and clinical studies have demonstrated that chronotherapy can significantly improve the therapeutic index of chemotherapeutic agents like cisplatin and 5-fluorouracil by enhancing anticancer activity and reducing toxicity. Further research is needed to elucidate the mechanisms underlying circadian regulation of cancer and to develop robust chronotherapeutic protocols tailored to individual patients’ circadian profiles, potentially transforming cancer care into more effective and personalized treatment strategies.
Breast cancer (BC) is one of the most common and fatal malignancies among women worldwide. Circadian rhythms have emerged in recent studies as being involved in the pathogenesis of breast cancer. In this paper, we reviewed the molecular mechanisms by which the dysregulation of the circadian genes impacts the development of BC, focusing on the critical clock genes, brain and muscle ARNT-like protein 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK). We discussed how the circadian rhythm disruption (CRD) changes the tumor microenvironment (TME), immune responses, inflammation, and angiogenesis. The CRD compromises immune surveillance and features and activities of immune effectors, including CD8+ T cells and tumor-associated macrophages, that are important in an effective anti-tumor response. Meanwhile, in this review, we discuss bidirectional interactions: age and circadian rhythms, aging further increases the risk of breast cancer through reduced vasoactive intestinal polypeptide (VIP), affecting suprachiasmatic nucleus (SCN) synchronization, reduced ability to repair damaged DNA, and weakened immunity. These complex interplays open new avenues toward targeted therapies by the combination of clock drugs with chronotherapy to potentiate the immune response while reducing tumor progression for better breast cancer outcomes. This review tries to cover the broad area of emerging knowledge on the tumor-immune nexus affected by the circadian rhythm in breast cancer.
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