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Modelling Physiological and Pharmacological Controlon Cell Proliferation to Optimise Cancer Treatments

Published online by Cambridge University Press:  05 June 2009

J. Clairambault
J. Clairambault*
Affiliation:
INRIA Paris-Rocquencourt, BANG project-team, BP 105, F78153 Le Chesnay Cedex
*
[email protected]
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Abstract

This review aims at presenting asynoptic, if not exhaustive, point of view on some of the problemsencountered by biologists and physicians who deal with naturalcell proliferation and disruptions of its physiological control incancer disease. It also aims at suggesting how mathematicians arenaturally challenged by these questions and how they might help,not only biologists to deal theoretically with biologicalcomplexity, but also physicians to optimise therapeutics, on whichlast point the focus will be set here. To this purpose,mathematical modelling should represent proliferating cellpopulation dynamics with natural built-in control targets (whichimplies modelling the cell division cycle), together with thedistribution of drugs in the organism and their molecular actionson different targets at the cell level on proliferation, i.e.,molecular pharmacokinetics-pharmacodynamics of antiproliferativedrugs. This should make possible optimal control of drug deliverywith constraints to be determined according to the mainpharmacological issues encountered in the clinic: unwanted toxicside-effects, occurrence of drug resistance. Mathematicalmodelling should also take into account physiological determinantsof cell and tissue proliferation, such as intervention of theimmune system, circadian control on cell cycle checkpointproteins, and activity of intracellular drug processing enzymestogether with individual variations in the activities of theseproteins (genetic polymorphism). Taking these points into accountwill add to the rich scenery of normal or disrupted cell andtissue regulations, and their corrections by drugs, a naturalenvironmental, whole body physiological, frame. It is necessaryindeed to consider such a framework if one wants to eventually beactually helpful to clinicians who routinely treat by combinationsof drugs living Humans with their complex whole body regulations,often dependent on genotypic variations, and not isolated cells ortissues.

Keywords

cell proliferationpopulation dynamicsphysiologically structured partial differential equationspharmacological controlpharmacokinetics-pharmacodynamicsphysiological modellingcancer treatmentstherapeuticoptimisationindividualised medicine
Type
Research Article
Information
Mathematical Modelling of Natural Phenomena , Volume 4 , Issue 3: Cancer modelling (Part 2) , 2009 , pp. 12 - 67
Copyright
© EDP Sciences, 2009

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