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Temporal Genomics for tailored chronotherapeutics

Obiettivo

Chronic diseases account for 75% of the disability-adjusted years in Europe and cause the premature death of 17 million people worldwide. Differences in aetiology as well as patient genetic origin, gender, age, lifestyle and biological time structure account for large variability in individual time courses of the same disease entity. Patient-tailored therapeutics is needed to prevent adverse events and improve overall therapeutic activity.
Rather than using pharmacogenomics for excluding patients from an active treatment option, TEMPO will combine functional genomics, proteomics, cell signalling, systems biology and pharmacokinetics to optimize therapeutic index in most individual patients. Thus TEMPO will determine 3 to 5 chronotherapeutics schedules with distinct temporal delivery patterns of the same anticancer drug. Each schedule is adjusted to a different dynamic class of temporal genomics and phenomics parameters related to interwoven circadian and cell division cycles and drug metabolism. In vivo, in vitro, in silico approaches are integrated through the multidisciplinary excellence in the consortium.
TEMPO will offer a proof of principle of tailored chronotherapeutics in mouse models for irinotecan, an active drug against colorectal cancers, and for seliciclib, currently in clinical testing. TEMPO will gather the corresponding human prerequisites and technology for subsequent application to patients. Three SMEs play a pivotal role for the impact of TEMPO on European health, economics and society. Novel and complementary in silico dynamic models of coordinated clock, cell cycle and pharmacology pathways will identify new therapeutic targets and delivery schedules of active molecules, thus improve drug development processes. New tools will enable personalized medicine to integrate the time dimension in routine implementation. TEMPO will reduce both therapeutic variability and attrition rates two major impediments for human health and pharmaceutical industry...

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FP6-2005-LIFESCIHEALTH-7
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Coordinatore

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
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Indirizzo
rue de Tolbiac 101
PARIS
Francia

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