Theoretical investigation of the efficacy of antiangiogenic drugs combined to chemotherapy in xenografted mice.

Floriane Lignet 1 Sébastien Benzekry 2 Shelby Wilson 1 Frédérique Billy 3 Olivier Saut 4 Michel Tod 5 Benoit You 5 A. Adda Berkane 6 S. Kassour 6 M. X. Wei 6 Emmanuel Grenier 1 Benjamin Ribba 1
1 NUMED - Numerical Medicine
UMPA-ENSL - Unité de Mathématiques Pures et Appliquées, Inria Grenoble - Rhône-Alpes
2 CCSB - Center of Cancer and Systems Biology
3 Evaluation et modélisation des effets thérapeutiques
Département biostatistiques et modélisation pour la santé et l'environnement [LBBE]
4 MC2 - Modélisation, contrôle et calcul
Inria Bordeaux - Sud-Ouest, UB - Université de Bordeaux, CNRS - Centre National de la Recherche Scientifique : UMR5251
5 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
6 ENVA - École nationale vétérinaire d'Alfort
Abstract : Antiangiogenic drugs were developed with the aim to inhibit the formation of intratumoral blood vessels and in consequence the growth of solid tumors. As these drugs are generally combined with classical cytotoxic drugs in the treatment of cancer patients, finding the optimal combinations remains a complex challenge due to possible interactions of the antiangiogenic compound with the hemodynamic property of the treated tumor. To analyze this problem, we developed a multi-scale model of vascular tumor growth combining a molecular model of VEGF signaling pathways and a tissue model of the tumor expansion including the dynamics of cellular and tissue processes of tumor growth and response to treatments. We addressed the potential impact of antiangiogenic drug by defining a new index of vasculature quality which depends on the balance between stable and unstable vessels within the tumor mass. Our goal was to investigate the interactions between a chemotherapy and a antiangiogenic treatment, and, by simulating the model, to identify the optimal delay of chemotherapy delivery after the administration of the antiangiogenic compound. This theoretical analysis could be used in the future to optimize antiangiogenic drug delivery in preclinical settings and to facilitate the translation from preclinical to clinical studies.
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Journal articles
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https://hal.inria.fr/hal-00785876
Contributor : Benjamin Ribba <>
Submitted on : Thursday, February 7, 2013 - 11:17:58 AM
Last modification on : Wednesday, November 20, 2019 - 2:36:17 AM

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Floriane Lignet, Sébastien Benzekry, Shelby Wilson, Frédérique Billy, Olivier Saut, et al.. Theoretical investigation of the efficacy of antiangiogenic drugs combined to chemotherapy in xenografted mice.. Journal of Theoretical Biology, Elsevier, 2013, 320, pp.86-99. ⟨10.1016/j.jtbi.2012.12.013⟩. ⟨hal-00785876⟩

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