TY  - JOUR
AU  - Ector, Carolin
AU  - Schmal, Christoph
AU  - Didier, Jeff
AU  - De Landtsheer, Sébastien
AU  - Schulte, Johannes H
AU  - Keilholz, Ulrich
AU  - Sauter, Thomas
AU  - Kramer, Achim
AU  - Herzel, Hanspeter
AU  - Granada, Adrián E
TI  - Circadian rhythm heterogeneity modulates drug response variations in neuroblastoma models.
JO  - Cell reports
VL  - 45
IS  - 2
SN  - 2211-1247
CY  - Maryland Heights, MO
PB  - Cell Press
M1  - DKFZ-2026-00360
SP  - 116975
PY  - 2026
N1  - #DKTKZFB9#
AB  - 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.
KW  - CP: cancer (Other)
KW  - CP: metabolism (Other)
KW  - cancer (Other)
KW  - chronotherapy (Other)
KW  - circadian clock (Other)
KW  - circadian rhythms (Other)
KW  - neuroblastoma (Other)
KW  - systems biology (Other)
KW  - time-of-day sensitivity (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41678337
DO  - DOI:10.1016/j.celrep.2026.116975
UR  - https://inrepo02.dkfz.de/record/309875
ER  -