[en] 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.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Ector, Carolin; Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Berlin, Germany ; Faculty of Life Sciences, Humboldt-Universität zu Berlin, Berlin, Germany
Schmal, Christoph; Institute for Theoretical Biology, Humboldt-Universität zu Berlin, Berlin, Germany
DIDIER, Jeff ; University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
DE LANDTSHEER, Sébastien ; University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
Finger, Anna-Marie ; Institute for Medical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany ; Department of Anatomy, University of California, San Francisco, San Francisco, CA, USA
Müller-Marquardt, Francesca; Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Berlin, Germany ; Institute of Research for Development, University of Montpellier, Montpellier, France
Schulte, Johannes H ; Department of Pediatric Oncology, Hematology and Stem Cell Transplantation, Charité - Universitätsmedizin Berlin, Berlin, Germany ; Clinic for Pediatrics and Adolescent Medicine, Universitätsklinikum Tübingen, Tübingen, Germany
SAUTER, Thomas ; University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
Keilholz, Ulrich; Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Berlin, Germany ; German Cancer Consortium (DKTK), Berlin, Germany
Herzel, Hanspeter; Institute for Theoretical Biology, Humboldt-Universität zu Berlin, Berlin, Germany ; Charité - Universitätsmedizin Berlin, Berlin, Germany
Kramer, Achim ; Institute for Medical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany
Granada, Adrián E ; Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Berlin, Germany. adrian.granada@charite.de ; German Cancer Consortium (DKTK), Berlin, Germany. adrian.granada@charite.de
External co-authors :
yes
Language :
English
Title :
Time-of-day effects of cancer drugs revealed by high-throughput deep phenotyping.
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