Circadian clock features define novel subtypes among breast cancer cells and shape drug sensitivity.

IF 8.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Molecular Systems Biology Pub Date : 2025-04-01 Epub Date: 2025-02-24 DOI:10.1038/s44320-025-00092-7
Carolin Ector, Jeff Didier, Sébastien De Landtsheer, Malthe S Nordentoft, Christoph Schmal, Ulrich Keilholz, Hanspeter Herzel, Achim Kramer, Thomas Sauter, Adrián E Granada
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引用次数: 0

Abstract

The circadian clock regulates key physiological processes, including cellular responses to DNA damage. Circadian-based therapeutic strategies optimize treatment timing to enhance drug efficacy and minimize side effects, offering potential for precision cancer treatment. However, applying these strategies in cancer remains limited due to a lack of understanding of the clock's function across cancer types and incomplete insights into how the circadian clock affects drug responses. To address this, we conducted deep circadian phenotyping across a panel of breast cancer cell lines. Observing diverse circadian dynamics, we characterized metrics to assess circadian rhythm strength and stability in vitro. This led to the identification of four distinct circadian-based phenotypes among 14 breast cancer cell models: functional, weak, unstable, and dysfunctional clocks. Furthermore, we demonstrate that the circadian clock plays a critical role in shaping pharmacological responses to various anti-cancer drugs and we identify circadian features descriptive of drug sensitivity. Collectively, our findings establish a foundation for implementing circadian-based treatment strategies in breast cancer, leveraging clock phenotypes and drug sensitivity patterns to optimize therapeutic outcomes.

生物钟特征定义了乳腺癌细胞中的新亚型并形成了药物敏感性。
生物钟调节关键的生理过程,包括细胞对DNA损伤的反应。基于昼夜节律的治疗策略优化了治疗时机,提高了药物疗效,最大限度地减少了副作用,为精确治疗癌症提供了可能。然而,由于缺乏对生物钟在不同癌症类型中的功能的了解,以及对生物钟如何影响药物反应的不完全了解,这些策略在癌症中的应用仍然有限。为了解决这个问题,我们对一组乳腺癌细胞系进行了深入的昼夜节律表型分析。观察不同的昼夜节律动态,我们描述了指标来评估体外昼夜节律的强度和稳定性。这导致在14种乳腺癌细胞模型中鉴定出四种不同的基于昼夜节律的表型:功能时钟、弱时钟、不稳定时钟和功能失调时钟。此外,我们证明了生物钟在形成对各种抗癌药物的药理反应中起着关键作用,我们确定了描述药物敏感性的昼夜节律特征。总的来说,我们的研究结果为在乳腺癌中实施基于昼夜节律的治疗策略奠定了基础,利用时钟表型和药物敏感性模式来优化治疗结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Systems Biology
Molecular Systems Biology 生物-生化与分子生物学
CiteScore
18.50
自引率
1.00%
发文量
62
审稿时长
6-12 weeks
期刊介绍: Systems biology is a field that aims to understand complex biological systems by studying their components and how they interact. It is an integrative discipline that seeks to explain the properties and behavior of these systems. Molecular Systems Biology is a scholarly journal that publishes top-notch research in the areas of systems biology, synthetic biology, and systems medicine. It is an open access journal, meaning that its content is freely available to readers, and it is peer-reviewed to ensure the quality of the published work.
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