通过高通量深度表型分析揭示癌症药物的时间效应。
Time-of-day effects of cancer drugs revealed by high-throughput deep phenotyping.
发表日期:2024 Aug 22
作者:
Carolin Ector, Christoph Schmal, Jeff Didier, Sébastien De Landtsheer, Anna-Marie Finger, Francesca Müller-Marquardt, Johannes H Schulte, Thomas Sauter, Ulrich Keilholz, Hanspeter Herzel, Achim Kramer, Adrián E Granada
来源:
Stem Cell Research & Therapy
摘要:
生物钟是一种基本的生物调节器,控制着健康和疾病的重要细胞过程。基于昼夜节律的治疗策略越来越被认为是有前途的途径。将药物给药与昼夜节律保持一致可以提高治疗效果并最大限度地减少副作用。然而,发现最佳治疗时机仍然具有挑战性,限制了其广泛采用。在这项工作中,我们引入了一种高通量方法,将实时成像和数据分析技术集成到深层表型癌细胞模型中,评估其昼夜节律、生长和药物反应。我们设计了一个简化的流程,用于分析一天中不同时间的药物敏感性,确定最佳治疗窗口和反应细胞类型和药物组合。最后,我们使用多种计算工具来揭示影响一天中不同时间药物敏感性的细胞和遗传因素。我们的多功能方法适用于各种生物模型,促进其广泛的应用和相关性。最终,这项研究利用昼夜节律来优化抗癌药物治疗,有望改善结果和变革性治疗策略。© 2024。作者。
The circadian clock, a fundamental biological regulator, governs essential cellular processes in health and disease. Circadian-based therapeutic strategies are increasingly gaining recognition as promising avenues. Aligning drug administration with the circadian rhythm can enhance treatment efficacy and minimize side effects. Yet, uncovering the optimal treatment timings remains challenging, limiting their widespread adoption. In this work, we introduce a high-throughput approach integrating live-imaging and data analysis techniques to deep-phenotype cancer cell models, evaluating their circadian rhythms, growth, and drug responses. We devise a streamlined process for profiling drug sensitivities across different times of the day, identifying optimal treatment windows and responsive cell types and drug combinations. Finally, we implement multiple computational tools to uncover cellular and genetic factors shaping time-of-day drug sensitivity. Our versatile approach is adaptable to various biological models, facilitating its broad application and relevance. Ultimately, this research leverages circadian rhythms to optimize anti-cancer drug treatments, promising improved outcomes and transformative treatment strategies.© 2024. The Author(s).