TY  - JOUR
AU  - Ector, Carolin
AU  - Didier, Jeff
AU  - De Landtsheer, Sébastien
AU  - Nordentoft, Malthe S
AU  - Schmal, Christoph
AU  - Keilholz, Ulrich
AU  - Herzel, Hanspeter
AU  - Kramer, Achim
AU  - Sauter, Thomas
AU  - Granada, Adrián E
TI  - Circadian clock features define novel subtypes among breast cancer cells and shape drug sensitivity.
JO  - Molecular systems biology
VL  - 21
IS  - 4
SN  - 1744-4292
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2025-00429
SP  - 315-340
PY  - 2025
N1  - 2025 Apr;21(4):315-340
AB  - The circadian clock regulates key physiological processes, including cellular responses to DNA damage. Circadian-based therapeutic strategies optimize treatment timing to enhance drug efficacy and minimize side effects, offering potential for precision cancer treatment. However, applying these strategies in cancer remains limited due to a lack of understanding of the clock's function across cancer types and incomplete insights into how the circadian clock affects drug responses. To address this, we conducted deep circadian phenotyping across a panel of breast cancer cell lines. Observing diverse circadian dynamics, we characterized metrics to assess circadian rhythm strength and stability in vitro. This led to the identification of four distinct circadian-based phenotypes among 14 breast cancer cell models: functional, weak, unstable, and dysfunctional clocks. Furthermore, we demonstrate that the circadian clock plays a critical role in shaping pharmacological responses to various anti-cancer drugs and we identify circadian features descriptive of drug sensitivity. Collectively, our findings establish a foundation for implementing circadian-based treatment strategies in breast cancer, leveraging clock phenotypes and drug sensitivity patterns to optimize therapeutic outcomes.
KW  - Breast Cancer (Other)
KW  - Circadian Clock (Other)
KW  - Circadian Medicine (Other)
KW  - Systems Biology (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39994450
DO  - DOI:10.1038/s44320-025-00092-7
UR  - https://inrepo02.dkfz.de/record/299469
ER  -