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@ARTICLE{Gutu:300146,
      author       = {N. Gutu and H. Ishikuma and C. Ector and U. Keilholz and H.
                      Herzel and A. E. Granada$^*$},
      title        = {{A} combined mathematical and experimental approach reveals
                      the drivers of time-of-day drug sensitivity in human cells.},
      journal      = {Communications biology},
      volume       = {8},
      number       = {1},
      issn         = {2399-3642},
      address      = {London},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2025-00637},
      pages        = {491},
      year         = {2025},
      abstract     = {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.},
      keywords     = {Humans / Circadian Clocks: drug effects / Antineoplastic
                      Agents: pharmacology / Neoplasms: drug therapy / Neoplasms:
                      pathology / Circadian Rhythm: drug effects / Cell Line,
                      Tumor / Models, Biological / Drug Resistance, Neoplasm /
                      Antineoplastic Agents (NLM Chemicals)},
      cin          = {BE01},
      ddc          = {570},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40133704},
      doi          = {10.1038/s42003-025-07931-1},
      url          = {https://inrepo02.dkfz.de/record/300146},
}