Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Sangareddy 502285, Telangana,India.
Curr Drug Metab. 2021;22(13):998-1008. doi: 10.2174/1389200222666211119103422.
Intrinsic rhythms in host and cancer cells play an imperative role in tumorigenesis and anticancer therapy. Circadian medicine in cancer is principally reliant on the control of growth and development of cancer cells or tissues by targeting the molecular clock and implementing time-of-day-based anticancer treatments for therapeutic improvements. In recent years, based on extensive high-throughput studies, we witnessed the arrival of several drugs and drug-like compounds that can modulate circadian timekeeping for therapeutic gain in cancer management.
This perspective article intends to illustrate the current trends in circadian medicine in cancer, focusing on clock-modulating pharmacological compounds and circadian regulation of anticancer drug metabolism and efficacy. Scope and Approach: Considering the critical roles of the circadian clock in metabolism, cell signaling, and apoptosis, chronopharmacology research is exceedingly enlightening for understanding cancer biology and improving anticancer therapeutics. In addition to reviewing the relevant literature, we investigated the rhythmic expression of molecular targets for many anticancer drugs frequently used to treat different cancer types. Key Findings and Conclusion: There are adequate empirical pieces of evidence supporting circadian regulation of drug metabolism, transport, and detoxification. Administration of anticancer drugs at specific dosing times can improve their effectiveness and reduce the toxic effects. Moreover, pharmacological modulators of the circadian clock could be used for targeted anticancer therapeutics such as boosting circadian rhythms in the host can markedly reduce the growth and viability of tumors. All in all, precision chronomedicine can offer multiple advantages over conventional anticancer therapy.
宿主和癌细胞的内在节律在肿瘤发生和抗癌治疗中起着至关重要的作用。癌症中的昼夜节律医学主要依赖于通过靶向分子钟控制癌细胞或组织的生长和发育，并实施基于时间的抗癌治疗以提高治疗效果。近年来，基于广泛的高通量研究，我们见证了几种可以调节昼夜节律计时以获得癌症管理治疗增益的时钟调节药理学化合物和药物样化合物的出现。
本文旨在阐述癌症中昼夜节律医学的当前趋势，重点介绍时钟调节药理学化合物以及昼夜节律对抗癌药物代谢和疗效的调节。
考虑到昼夜节律钟在代谢、细胞信号转导和细胞凋亡中的关键作用，时间药理学研究对于理解癌症生物学和改善抗癌治疗极具启发性。除了回顾相关文献外，我们还研究了许多常用于治疗不同癌症类型的抗癌药物的分子靶标在节律上的表达。
有充分的经验证据支持药物代谢、转运和解毒的昼夜节律调节。在特定的给药时间给予抗癌药物可以提高其疗效并降低毒性作用。此外，昼夜节律钟的药理学调节剂可用于靶向抗癌治疗，例如增强宿主的昼夜节律可以显著降低肿瘤的生长和活力。总之，精准时间医学可以为常规抗癌治疗提供多种优势。
