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Circadian timing in cancer treatments

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Lévi, Francis A., Okyar, Alper, Dulong, Sandrine, Innominato, Pasquale F. and Clairambault, Jean (2010) Circadian timing in cancer treatments. Annual Review of Pharmacology and Toxicology, Volume 50 (Number 1). pp. 377-421. doi:10.1146/annurev.pharmtox.48.113006.094626 ISSN 0362-1642.

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Official URL: http://dx.doi.org/10.1146/annurev.pharmtox.48.1130...

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Abstract

The circadian timing system is composed of molecular clocks, which drive 24-h changes in xenobiotic metabolism and detoxification, cell cycle events, DNA repair, apoptosis, and angiogenesis. The cellular circadian clocks are coordinated by endogenous physiological rhythms, so that they tick in synchrony in the host tissues that can be damaged by anticancer agents. As a result, circadian timing can modify 2- to 10-fold the tolerability of anticancer medications in experimental models and in cancer patients. Improved efficacy is also seen when drugs are given near their respective times of best tolerability, due to (a) inherently poor circadian entrainment of tumors and (b) persistent circadian entrainment of healthy tissues. Conversely, host clocks are disrupted whenever anticancer drugs are administered at their most toxic time. On the other hand, circadian disruption accelerates experimental and clinical cancer processes. Gender, circadian physiology, clock genes, and cell cycle critically affect outcome on cancer chronotherapeutics. Mathematical and systems biology approaches currently develop and integrate theoretical, experimental, and technological tools in order to further optimize and personalize the circadian administration of cancer treatments.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
R Medicine > RC Internal medicine
R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016)
Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Circadian rhythms, Antineoplastic agents, Cancer--Chemotherapy
Journal or Publication Title: Annual Review of Pharmacology and Toxicology
Publisher: Annual Reviews
ISSN: 0362-1642
Official Date: February 2010
Dates:
DateEvent
February 2010Published
Volume: Volume 50
Number: Number 1
Number of Pages: 45
Page Range: pp. 377-421
DOI: 10.1146/annurev.pharmtox.48.113006.094626
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: EU Network of Excellence on Biosimulation (BIOSIM), Specific Targeted Research Project TEMPO, Specific Support Action PROUST, Association Internationale pour la Recherche sur le Temps Biologique et la Chronothérapie (ARTBC International), Türkiye Bilimsel ve Teknolojik Arastirma Kurumu [Scientific and Technological Research Council of Turkey] (TÜBITAK), Hôpital Universitaire Paul Brousse (Villejuif, France)
Grant number: LSHBCT-2004-005137 (BIOSIM) ; LSHG-ct-2006-037543 (TEMPO) ; LSSG-CT-2006-037654 (PROUST)

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