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A circadian clock transcription model for the personalization of cancer chronotherapy
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Li, X. -M., Mohammad-Djafari, A., Dumitru, M., Dulong, S., Filipski, E., Siffroi-Fernandez, S., Mteyrek, A., Scaglione, F., Guettier, C., Delaunay, F. and Lévi, Francis A. (2013) A circadian clock transcription model for the personalization of cancer chronotherapy. Cancer Research, Volume 73 (Number 24). pp. 7176-7188. doi:10.1158/0008-5472.CAN-13-1528
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Official URL: http://dx.doi.org/10.1158/0008-5472.can-13-1528
Abstract
Circadian timing of anticancer medications has improved treatment tolerability and efficacy several fold, yet with intersubject variability. Using three C57BL/6-based mouse strains of both sexes, we identified three chronotoxicity classes with distinct circadian toxicity patterns of irinotecan, a topoisomerase I inhibitor active against colorectal cancer. Liver and colon circadian 24-hour expression patterns of clock genes Rev-erbα and Bmal1 best discriminated these chronotoxicity classes, among 27 transcriptional 24-hour time series, according to sparse linear discriminant analysis. An 8-hour phase advance was found both for Rev-erbα and Bmal1 mRNA expressions and for irinotecan chronotoxicity in clock-altered Per2m/m mice. The application of a maximum-a-posteriori Bayesian inference method identified a linear model based on Rev-erbα and Bmal1 circadian expressions that accurately predicted for optimal irinotecan timing. The assessment of the Rev-erbα and Bmal1 regulatory transcription loop in the molecular clock could critically improve the tolerability of chemotherapy through a mathematical model–based determination of host-specific optimal timing. Cancer Res; 73(24); 7176–88. ©2013 AACR.
| Item Type: | Journal Article | ||||||||||
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| Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica |
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| Divisions: | Faculty of Medicine > Warwick Medical School | ||||||||||
| Library of Congress Subject Headings (LCSH): | Circadian rhythms, Circadian rhythms--Effect of chemicals on, Chemotherapy, Antineoplastic agents | ||||||||||
| Journal or Publication Title: | Cancer Research | ||||||||||
| Publisher: | American Association for Cancer Research | ||||||||||
| ISSN: | 0008-5472 | ||||||||||
| Official Date: | 15 December 2013 | ||||||||||
| Dates: |
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| Volume: | Volume 73 | ||||||||||
| Number: | Number 24 | ||||||||||
| Number of Pages: | 13 | ||||||||||
| Page Range: | pp. 7176-7188 | ||||||||||
| DOI: | 10.1158/0008-5472.CAN-13-1528 | ||||||||||
| Status: | Peer Reviewed | ||||||||||
| Publication Status: | Published | ||||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||||
| Funder: | European Union (EU), ERASysBio, Association pour la Recherche sur le Temps Biologique et la Chronothérapie (ARTBC) | ||||||||||
| Grant number: | LSHG-CT-2006-037543 (EU), ANR 2009-SYSB-002-01-04 (ERASysBio) |
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