Gutu Nica, Ishikuma Hitoshi, Ector Carolin, Keilholz Ulrich, Herzel Hanspeter, Granada Adrián E
Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Humboldt Universität zu Berlin, Berlin, Germany.
Commun Biol. 2025 Mar 25;8(1):491. doi: 10.1038/s42003-025-07931-1.
The circadian clock plays a pivotal role in regulating various aspects of cancer, influencing tumor growth and treatment responses. There are significant changes in drug efficacy and adverse effects when drugs are administered at different times of the day, underscoring the importance of considering the time of day in treatments. Despite these well-established findings, chronotherapy approaches in drug treatment have yet to fully integrate into clinical practice, largely due to the stringent clinical requirements for proving efficacy and safety, alongside the need for deeper mechanistic insights. In this study, we employ a combined mathematical and experimental approach to systematically investigate the factors influencing time-of-day drug sensitivity in human cells. Here we show how circadian and drug properties independently shape time-of-day profiles, providing valuable insights into the temporal dynamics of treatment responses. Understanding how drug efficacy fluctuates throughout the day holds immense potential for the development of personalized treatment strategies aligned with an individual's internal biological clock, revolutionizing cancer treatment by maximizing therapeutic benefits. Moreover, our framework offers a promising avenue for refining future drug screening efforts, paving the way for more effective and targeted therapies across diverse tissue types.
生物钟在调节癌症的各个方面起着关键作用，影响肿瘤生长和治疗反应。当在一天中的不同时间给药时，药物疗效和不良反应会有显著变化，这突出了在治疗中考虑给药时间的重要性。尽管有这些已被充分证实的发现，但药物治疗中的时间疗法尚未完全融入临床实践，这主要是由于证明疗效和安全性的严格临床要求，以及需要更深入的机制见解。在本研究中，我们采用数学和实验相结合的方法，系统地研究影响人类细胞中一天中不同时间药物敏感性的因素。在这里，我们展示了生物钟和药物特性如何独立塑造一天中不同时间的特征，为治疗反应的时间动态提供了有价值的见解。了解药物疗效如何在一天中波动，对于制定与个体内部生物钟相一致的个性化治疗策略具有巨大潜力，通过最大化治疗益处彻底改变癌症治疗。此外，我们的框架为改进未来的药物筛选工作提供了一条有前景的途径，为跨多种组织类型的更有效和靶向治疗铺平道路。
