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000309875 1001_ $$aEctor, Carolin$$b0
000309875 245__ $$aCircadian rhythm heterogeneity modulates drug response variations in neuroblastoma models.
000309875 260__ $$aMaryland Heights, MO$$bCell Press$$c2026
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000309875 520__ $$aCircadian clocks regulate essential cellular functions and influence cancer development and treatment outcomes. Aligning therapy with circadian rhythms can improve efficacy and reduce toxicity, yet whether neuroblastoma, a heterogeneous pediatric tumor, maintains circadian function remains unclear. Here, we systematically profiled circadian dynamics across 12 neuroblastoma cell models using long-term bioluminescence assays and computational analysis. Our findings reveal heterogeneous circadian patterns ranging from robust to arrhythmic, which we linked to distinct neuroblastoma genetic features. By integrating drug sensitivity data, we identified candidate compounds whose effectiveness correlates with circadian expression profiles. Moreover, time-of-day treatment assays with the ALK inhibitor lorlatinib and frontline chemotherapeutics revealed distinct temporal drug responses that were more pronounced in circadian-competent than weakly rhythmic cell lines. Together, these findings establish circadian heterogeneity as a previously unrecognized dimension of neuroblastoma biology and highlight the therapeutic potential of chronotherapy approaches for improved treatment efficacy.
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000309875 650_7 $$2Other$$aCP: cancer
000309875 650_7 $$2Other$$aCP: metabolism
000309875 650_7 $$2Other$$acancer
000309875 650_7 $$2Other$$achronotherapy
000309875 650_7 $$2Other$$acircadian clock
000309875 650_7 $$2Other$$acircadian rhythms
000309875 650_7 $$2Other$$aneuroblastoma
000309875 650_7 $$2Other$$asystems biology
000309875 650_7 $$2Other$$atime-of-day sensitivity
000309875 7001_ $$aSchmal, Christoph$$b1
000309875 7001_ $$aDidier, Jeff$$b2
000309875 7001_ $$aDe Landtsheer, Sébastien$$b3
000309875 7001_ $$aSchulte, Johannes H$$b4
000309875 7001_ $$0P:(DE-He78)db014277a1d4005afd93fa95bc6a1001$$aKeilholz, Ulrich$$b5
000309875 7001_ $$aSauter, Thomas$$b6
000309875 7001_ $$aKramer, Achim$$b7
000309875 7001_ $$aHerzel, Hanspeter$$b8
000309875 7001_ $$aGranada, Adrián E$$b9
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