El-Tanani Mohamed, Rabbani Syed Arman, Ali Areeg Anwer, Alfaouri Ibrahim Ghaleb Ali, Al Nsairat Hamdi, Al-Ani Israa Hamid, Aljabali Alaa A, Rizzo Manfredi, Patoulias Dimitrios, Khan Mohammad Ahmed, Parvez Suhel, El-Tanani Yahia
RAK College of Pharmacy, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates.
Translational and Medical Research Centre (TMRC), Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates.
Discov Oncol. 2024 Dec 18;15(1):767. doi: 10.1007/s12672-024-01643-4.
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.
昼夜节律是大约24小时的内在循环，调节着许多生理过程，包括睡眠-觉醒周期、激素释放和新陈代谢。这些节律由昼夜节律钟协调，昼夜节律钟主要位于下丘脑的视交叉上核（SCN）。昼夜节律的破坏，无论是由于基因突变、环境因素还是生活方式的选择，都可能对健康产生重大影响，导致睡眠障碍、代谢综合征和心血管疾病等疾病。此外，昼夜节律的破坏与各种癌症的发生之间存在着深刻的联系，对疾病的发病率和进展有影响。昼夜节律钟对这些途径的调节在肿瘤发生中具有重要意义，如细胞周期控制、DNA损伤反应、细胞凋亡和新陈代谢。此外，昼夜节律系统调节癌症治疗的疗效和毒性。在癌症治疗中，使用时间疗法来优化医疗治疗的时间，包括在特定间隔进行化疗、放疗或其他治疗干预，以提高疗效并将副作用降至最低。这种方法利用了细胞过程中的昼夜变化，包括DNA修复、细胞周期进程和药物代谢。临床前和临床研究表明，时间疗法可以通过增强抗癌活性和降低毒性，显著提高顺铂和5-氟尿嘧啶等化疗药物的治疗指数。需要进一步研究以阐明癌症昼夜调节的潜在机制，并制定针对个体患者昼夜节律特征的强有力的时间治疗方案，这可能会将癌症治疗转变为更有效和个性化的治疗策略。
