| Chronotherapy (TEMPO project) TEMPO is a strep project funded through the 6th European Community Framework Programme for Research, Technological Development and Demonstration (FP6) addressing the issue of the interactions between pharmacogenomics determinants of drug activity and two essential biological cycles for chronic disease processes, i.e. the circadian clock and the cell cycle.
Cell physiology is regulated by a 24-hour circadian clock. This clock is endogenously generated but influenced by external stimuli, in particular the ‘dark-light’ cycle, hence its “circadian clock” name. Circadian rhythms are particularly important in determining the rest-activity patterns of human beings, but also govern hormone production and cell division. Remarkably, healthy and tumour cells do not show the same rhythmicity. Cell division time of cancer cells often differs from healthy cells, due to loss of synchronisation between cells in the cycle. Moreover, the pharmacokinetic and pharmacosensitivity to drugs is also influenced by circadian rhythms. By taking advantage of the circadian rhythms of cell physiology, cancer chronotherapy aims at improving the antitumour efficacy of drugs when cancer cells are the most sensitive, whereas decreasing their toxicological effects, by administrating a drug at circadian times when it is best tolerated by the organism. Chronotherapeutics has already been used successfully in early clinical trials, as well as in Phase III clinical trials.
Physiomics plc is involved in several areas of the project (‘workpackages’), which include integration and mathematical modelling of the circadian timing system coupled to the cell cycle, PD and combined PK-PD analysis of drug delivery and the determination of optimal dynamic drug delivery schedules in human. Using its dedicated mathematical and computational technologies, Physiomics is an essential partner in addressing complex dynamic issues in chronotherapeutics modelling. This will improve and individualise drug doses and schedules, leading to tailored chronotherapeutics for selected anti-cancer drugs. For more information on this work please contact us.
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