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A Computational Framework to Assess the Efficacy of CytotoxicMolecules and Vascular Disrupting Agents against Solid Tumours

Published online by Cambridge University Press:  25 January 2012

M. Pons-Salort ,
B. van der Sanden ,
A. Juhem ,
A. Popov  and
A. Stéphanou
M. Pons-Salort
Affiliation:
UJF-Grenoble 1, CNRS, Laboratory TIMC-IMAG UMR 5525 DyCTiM research team, 38041 Grenoble, France
B. van der Sanden
Affiliation:
INSERM U836, Grenoble Institut des Neurosciences, UJF-Grenoble 1 CHU Michallon, 38042 Grenoble, France
A. Juhem
Affiliation:
Ecrins therapeutics, BIOPOLIS, 38700 La Tronche, France
A. Popov
Affiliation:
Ecrins therapeutics, BIOPOLIS, 38700 La Tronche, France
A. Stéphanou*
Affiliation:
UJF-Grenoble 1, CNRS, Laboratory TIMC-IMAG UMR 5525 DyCTiM research team, 38041 Grenoble, France
*
⋆Corresponding author. E-mail: Angelique.Stephanou@imag.fr
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Abstract

A computational framework for testing the effects of cytotoxic molecules, specific to agiven phase of the cell cycle, and vascular disrupting agents (VDAs) is presented. Themodel is based on a cellular automaton to describe tumour cell states transitions fromproliferation to death. It is coupled with a model describing the tumour vasculature andits adaptation to the blood rheological constraints when alterations are induced by VDAstreatment. Several therapeutic protocols in two structurally different vascular networkswere tested by varying the duration of cytotoxic drug perfusion and the periodicity oftreatment cycles. The impact of VDAs were also tested both experimentally from intravitalmicroscopy through a dorsal skinfold chamber on a mouse and numerically. Simulationresults show that combining cytotoxic treatment with a post treatment of VDA through ajudicious timing could favour the rapid eradication of the tumour. The computationalframework thus gives some insights into the outcome of cytotoxic and VDAs treatments on aqualitative basis. Future validation from our experimental setup could open up newperspectives towards Computer-Assisted Therapeutic Strategies.

Keywords

computational modellingcellular automatoncytotoxic moleculesvascular disrupting agentsvascular tumour growththerapeutic protocols
Type
Research Article
Information
Mathematical Modelling of Natural Phenomena , Volume 7 , Issue 1: Cancer modeling , 2012 , pp. 49 - 77
Copyright
© EDP Sciences, 2012

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