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Cited by 339

The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.

Systems Chronotherapeutics

Open access
Ballesta, Annabelle, Innominato, Pasquale F., Dallmann, Robert, Rand, David A., Lévi, Francis A.·2017·Pharmacological Reviews
DOI 10.1124/pr.116.013441
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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.

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Metadata

Authors
Ballesta, A., Innominato, P. F., Dallmann, R., Rand, D. A., & Lévi, F. A.
Venue
Pharmacological Reviews
Publisher
Elsevier BV
Published
2017-04
Volume
69
Issue
2
Pages
161-199
ISSN
0031-6997 (ISSN-L)
DOI
10.1124/pr.116.013441
OpenAlex
W4211057115
Cited by
339
References
44
FWCI
16.80
Type
journal article
Language
en
Open access
hybrid

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