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Cancer Causes & Control
Published in: Cancer Causes & Control 4/2006

01-05-2006 | Special Section on Cancer and Rhythm

Chronotherapeutics: The Relevance of Timing in Cancer Therapy

Author: Francis Lévi

Published in: Cancer Causes & Control | Issue 4/2006

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Abstract

Background

Cell physiology is regulated along the 24-h time scale by a circadian timing system composed of molecular clocks within each cell and a central coordination system in the brain. The mammalian molecular clock is made of interconnected molecular loops involving at least 12 circadian genes. The cellular clocks are coordinated by the suprachiasmatic nuclei, a hypothalamic pacemaker which also helps the organism adjust to environmental cycles. The rest–activity rhythm is a reliable marker of the circadian system function in both rodents and man. This circadian organization is responsible for predictable changes in the tolerability and efficacy of anticancer agents, and possibly also in tumor promotion or growth.

Methods

Expected least toxic times of chemotherapy were extrapolated from experimental models to human subjects with reference to the rest–activity cycle. The clinical relevance of the chronotherapy principle, i.e. treatment administration as a function of rhythms, has been demonstrated in randomized multicenter trials.

Results

Chronotherapeutic schedules have been used to safely document the activity of the association of oxaliplatin, 5-FU and leucovorin against metastatic colorectal cancer and to set up a new medicosurgical management of this disease which achieved unprecedented long term survival.

Conclusion

The chronotherapy concept offers further promises for improving current cancer treatment options as well as for optimizing the development of new anticancer or supportive agents
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Metadata
Title
Chronotherapeutics: The Relevance of Timing in Cancer Therapy
Author
Francis Lévi
Publication date
01-05-2006
Publisher
Kluwer Academic Publishers
Published in
Cancer Causes & Control / Issue 4/2006
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-005-9004-7

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