A Step Toward Optimization of Cancer Therapeutics [Chronobiological Investigations]

Inst. Nat. de Recherche en Inf. et en Autom., Rocquencourt
IEEE Engineering in Medicine and Biology Magazine (Impact Factor: 26.3). 02/2008; DOI: 10.1109/MEMB.2007.907363
Source: IEEE Xplore

ABSTRACT An integrative physiology model has been designed, which takes into account the cell proliferation at the level of a population of cells by age-structured partial differential equations (PDEs), its control by cell cycle proteins, and the control of these molecular mechanisms by the circadian system, designed as a network of coupled oscillators also described by ODEs. Cancer growth and response to therapy by anticancer drugs have been shown to be dependent on circadian clock inputs. This multiscale modeling framework will provide clinicians with a theoretical tool to bridge the gap between the pharmaceutical clinical control level and the molecular pharmacological hidden level of drug action.

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    ABSTRACT: We study proliferation in tissues from the point of view of physiologically structured partial differential models, focusing on age synchronisation in the cell division cycle in cell populations and its control at phase transition checkpoints. We show how a recent fluorescence-based technique (FUCCI) performed at the single cell level in proliferating cell populations allows identifying model parameters and how it may be applied to investigate healthy and cancer cell populations. We show how this modelling approach allows designing original optimisation methods for cancer chronotherapeutics, by controlling eigenvalues of differential operators underlying proliferation dynamics, in tumour and in healthy cell populations.
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