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@ARTICLE{Ector:309875,
      author       = {C. Ector and C. Schmal and J. Didier and S. De Landtsheer
                      and J. H. Schulte and U. Keilholz$^*$ and T. Sauter and A.
                      Kramer and H. Herzel and A. E. Granada},
      title        = {{C}ircadian rhythm heterogeneity modulates drug response
                      variations in neuroblastoma models.},
      journal      = {Cell reports},
      volume       = {45},
      number       = {2},
      issn         = {2211-1247},
      address      = {Maryland Heights, MO},
      publisher    = {Cell Press},
      reportid     = {DKFZ-2026-00360},
      pages        = {116975},
      year         = {2026},
      note         = {#DKTKZFB9#},
      abstract     = {Circadian clocks regulate essential cellular functions and
                      influence cancer development and treatment outcomes.
                      Aligning therapy with circadian rhythms can improve efficacy
                      and reduce toxicity, yet whether neuroblastoma, a
                      heterogeneous pediatric tumor, maintains circadian function
                      remains unclear. Here, we systematically profiled circadian
                      dynamics across 12 neuroblastoma cell models using long-term
                      bioluminescence assays and computational analysis. Our
                      findings reveal heterogeneous circadian patterns ranging
                      from robust to arrhythmic, which we linked to distinct
                      neuroblastoma genetic features. By integrating drug
                      sensitivity data, we identified candidate compounds whose
                      effectiveness correlates with circadian expression profiles.
                      Moreover, time-of-day treatment assays with the ALK
                      inhibitor lorlatinib and frontline chemotherapeutics
                      revealed distinct temporal drug responses that were more
                      pronounced in circadian-competent than weakly rhythmic cell
                      lines. Together, these findings establish circadian
                      heterogeneity as a previously unrecognized dimension of
                      neuroblastoma biology and highlight the therapeutic
                      potential of chronotherapy approaches for improved treatment
                      efficacy.},
      keywords     = {CP: cancer (Other) / CP: metabolism (Other) / cancer
                      (Other) / chronotherapy (Other) / circadian clock (Other) /
                      circadian rhythms (Other) / neuroblastoma (Other) / systems
                      biology (Other) / time-of-day sensitivity (Other)},
      cin          = {BE01},
      ddc          = {610},
      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:41678337},
      doi          = {10.1016/j.celrep.2026.116975},
      url          = {https://inrepo02.dkfz.de/record/309875},
}