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Dedicated experimental models addressing circadian clock,<br />
cell cycle and drug pharmacology issues will allow to dissect<br />
the molecular and signalling mechanisms that underlie<br />
optimal therapeutic schedules for both agents. Dedicated<br />
mathematical and computational methods will address<br />
complex dynamic issues in chronotherapeutics delivery<br />
modelling, based on already existing computational models<br />
for the mammalian circadian clock, the cell division<br />
cycle and anticancer drug pharmacology.<br />
Expected results<br />
TEMPO combines functional genomics, proteomics, cell<br />
signalling, systems biology and pharmacokinetics to optimize<br />
therapeutic index in patients. TEMPO will determine<br />
chronotherapeutics schedules with distinct temporal delivery<br />
patterns of the same anticancer drug. Each schedule is<br />
adjusted to a diff erent dynamic class of temporal genomics<br />
and phenomics parameters related to interwoven<br />
circadian and cell division cycles and drug metabolism.<br />
In vivo, in vitro and in silico approaches are integrated<br />
through the multidisciplinary excellence in the consortium.<br />
TEMPO will off er a proof of principle of tailored chronotherapeutics<br />
in mouse models for an active drugs against<br />
colorectal cancers.<br />
In silico dynamic models of coordinated clock, cell cycle and<br />
pharmacology pathways will identify new therapeutic targets<br />
and delivery schedules of active molecules. TEMPO will<br />
provide tools to reduce both therapeutic variability and<br />
attrition rates. New tools will enable personalized medicine<br />
to integrate the time dimension in routine implementation.<br />
Potential applications<br />
TEMPO will give the clues to implement research results into<br />
clinical applications. Through the identifi cation of nodal<br />
points in the interplay between the circadian timing system,<br />
the cell division cycle and drug pharmacology determinants,<br />
TEMPO will provide key information for potential targeted<br />
drug developments.<br />
TEMPO allows foreseeing a new opportunity for costeff<br />
ective medical progress through the real development<br />
of ambulatory medicine with direct relevance to the quality<br />
of life of cancer patients.<br />
The reduction of side eff ects and the improvement of antitumour<br />
activity is particularly important in women and in<br />
elderly patients who experience nearly 20 % more side<br />
eff ects from chemotherapy than men or younger adults.<br />
218<br />
Coordinator<br />
Francis Lévi<br />
Institut National de La Santé<br />
et de la Recherche Médicale<br />
INSERM U776 – Rythmes<br />
biologiques et cancers<br />
Hôpital Paul Brousse<br />
Avenue Paul-Vaillant Couturier 14<br />
94807 Villejuif, France<br />
levi-f@vjf.inserm.fr<br />
Partners<br />
Franck Delaunay<br />
CNRS<br />
Université de Nice – CNRS UMR 6348<br />
Bâtiment de Sciences Naturelles<br />
28 avenue Valrose<br />
06 108 Nice cedex 2, France<br />
delaunay@unice.fr<br />
Laurent Meijer<br />
Station Biologique – Amyloïds and Cell<br />
Division Cycle (ACDC) – CNRS<br />
Place Georges Teissier, B.P.74<br />
29682 Roscoff cedex, France<br />
meijer@sb-roscoff.fr<br />
Jean Clairambault<br />
INRIA<br />
INRIA Rocquencourt <strong>Research</strong> Unit<br />
Teams Bang and Contraintes<br />
Domaine de Voluceau – Rocquencourt<br />
78153 – PO Box 105 – Le Chesnay, France<br />
Jean.Clairambault@inria.fr<br />
Project number<br />
LSHG-CT-2006-037543<br />
EC contribution<br />
€ 2 086 720<br />
Duration<br />
36 months<br />
Starting date<br />
01/10/2006<br />
Instrument<br />
STREP<br />
Project website<br />
www.chrono-tempo.org<br />
Stefano Iacobelli<br />
CINBO<br />
Consorzio Interuniversitario Nazionale<br />
per la Bio-oncologia<br />
Laboratory of Molecular Oncology<br />
Center of Excellence on Aging Ce.S.I.<br />
C.E.S.I. via Colle Dell’Ara’<br />
66100 Chieti, Italy<br />
iacobell@unich.it<br />
Marco Pirovano<br />
H.S. Hospital Services S.p.A<br />
Villa delle Vallis snc<br />
Therapeutic delivery<br />
04011 Aprilia (Latina), Italy<br />
marco.pirovano@noctilo.it<br />
Jean-Baptiste Dumas<br />
Milne Edwards<br />
Helios Biosciences SARL<br />
8 Avenue du Général Sarrail<br />
94010 Créteil, France<br />
jb@heliosbiosciences.com<br />
Christophe Chassagnole<br />
Physiomics PLC<br />
The Magdalen Centre<br />
The Oxford Science Park<br />
OX4 4GA Oxford, United Kingdom<br />
cchassagnole@physiomics-plc.com<br />
Isabelle Geahel<br />
Inserm Transfert<br />
7 rue Watt<br />
75013 Paris, France<br />
Isabelle.geahel@inserm-transfert.fr<br />
CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
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