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Ballesta, Annabelle, Innominato, Pasquale F., Dallmann, Robert, Rand, D. A. (David A.) and Lévi, Francis A. (2017) Systems chronotherapeutics. Pharmacological Reviews, 69 (2). pp. 161-199. doi:10.1124/pr.116.013441
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Official URL: http://dx.doi.org/10.1124/pr.116.013441
Abstract
Chronotherapeutics aim at treating illnesses according to the endogenous biologic rhythms, which moderate xenobiotic metabolism and cellular drug response. The molecular clocks present in individual cells involve approximately fifteen clock genes interconnected in regulatory feedback loops. They are coordinated by the suprachiasmatic nuclei, a hypothalamic pacemaker, which also adjusts the circadian rhythms to environmental cycles. As a result, many mechanisms of diseases and drug effects are controlled by the circadian timing system. Thus, the tolerability of nearly 500 medications varies by up to fivefold according to circadian scheduling, both in experimental models and/or patients. Moreover, treatment itself disrupted, maintained, or improved the circadian timing system as a function of drug timing. Improved patient outcomes on circadian-based treatments (chronotherapy) have been demonstrated in randomized clinical trials, especially for cancer and inflammatory diseases. However, recent technological advances have highlighted large interpatient differences in circadian functions resulting in significant variability in chronotherapy response. Such findings advocate for the advancement of personalized chronotherapeutics through interdisciplinary systems approaches. Thus, the combination of mathematical, statistical, technological, experimental, and clinical expertise is now shaping the development of dedicated devices and diagnostic and delivery algorithms enabling treatment individualization. In particular, multiscale systems chronopharmacology approaches currently combine mathematical modeling based on cellular and whole-body physiology to preclinical and clinical investigations toward the design of patient-tailored chronotherapies. We review recent systems research works aiming to the individualization of disease treatment, with emphasis on both cancer management and circadian timing system–resetting strategies for improving chronic disease control and patient outcomes.
| Item Type: | Journal Article | ||||||
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| Subjects: | Q Science > QP Physiology R Medicine > RM Therapeutics. Pharmacology |
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| Divisions: | Faculty of Science > Mathematics Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Chronopharmacology , Circadian rhythms | ||||||
| Journal or Publication Title: | Pharmacological Reviews | ||||||
| Publisher: | American Society for Pharmacology and Experimental Therapeutics | ||||||
| ISSN: | 0031-6997 | ||||||
| Official Date: | 28 March 2017 | ||||||
| Dates: |
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| Date of first compliant deposit: | 8 June 2017 | ||||||
| Volume: | 69 | ||||||
| Number: | 2 | ||||||
| Page Range: | pp. 161-199 | ||||||
| DOI: | 10.1124/pr.116.013441 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Open Access | ||||||
| Funder: | Seventh Framework Programme (European Commission) (FP7), Cancer Research UK (CRUK) | ||||||
| Grant number: | Grant 305033 (FP7), Grant C53561/A19933 (CRUK) |
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