Time-of-day effects of cancer drugs revealed by high-throughput deep phenotyping

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 and Adrián E. Granada ()
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Carolin Ector: Charité – Universitätsmedizin Berlin
Christoph Schmal: Humboldt-Universität zu Berlin
Jeff Didier: University of Luxembourg
Sébastien De Landtsheer: University of Luxembourg
Anna-Marie Finger: Charité – Universitätsmedizin Berlin
Francesca Müller-Marquardt: Charité – Universitätsmedizin Berlin
Johannes H. Schulte: Charité – Universitätsmedizin Berlin
Thomas Sauter: University of Luxembourg
Ulrich Keilholz: Charité – Universitätsmedizin Berlin
Hanspeter Herzel: Humboldt-Universität zu Berlin
Achim Kramer: Charité – Universitätsmedizin Berlin
Adrián E. Granada: Charité – Universitätsmedizin Berlin

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-51611-3

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