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A pharmacologically based multiscale mathematical model of angiogenesis and its use in investigating the efficacy of a new cancer treatment strategy.

hal.structure.identifierLaboratoire d'Études Aérodynamiques [LEA]
dc.contributor.authorBILLY, Frédérique
hal.structure.identifierLaboratoire de Biométrie et Biologie Evolutive - UMR 5558 [LBBE]
hal.structure.identifierNumerical Medicine [NUMED]
dc.contributor.authorRIBBA, Benjamin
hal.structure.identifierInstitut de Mathématiques de Bordeaux [IMB]
hal.structure.identifierModélisation, contrôle et calcul [MC2]
dc.contributor.authorSAUT, Olivier
dc.contributor.authorMORRE-TROUILHET, Hélène
hal.structure.identifierInstitut de Mathématiques de Bordeaux [IMB]
hal.structure.identifierModélisation, contrôle et calcul [MC2]
dc.contributor.authorCOLIN, Thierry
hal.structure.identifierLaboratoire de Mathématiques [LAMA]
dc.contributor.authorBRESCH, Didier
hal.structure.identifierEvaluation et modélisation des effets thérapeutiques
dc.contributor.authorBOISSEL, Jean-Pierre
hal.structure.identifierNumerical Medicine [NUMED]
dc.contributor.authorGRENIER, Emmanuel
hal.structure.identifierBioinformatique, phylogénie et génomique évolutive [BPGE]
dc.contributor.authorFLANDROIS, Jean-Pierre
dc.date.issued2009-10-21
dc.identifier.issn0022-5193
dc.description.abstractEnTumor angiogenesis is the process by which new blood vessels are formed and enhance the oxygenation and growth of tumors. As angiogenesis is recognized as being a critical event in cancer development, considerable efforts have been made to identify inhibitors of this process. Cytostatic treatments that target the molecular events of the angiogenesis process have been developed, and have met with some success. However, it is usually difficult to preclinically assess the effectiveness of targeted therapies, and apparently promising compounds sometimes fail in clinical trials. We have developed a multiscale mathematical model of angiogenesis and tumor growth. At the molecular level, the model focuses on molecular competition between pro- and anti-angiogenic substances modeled on the basis of pharmacological laws. At the tissue scale, the model uses partial differential equations to describe the spatio-temporal changes in cancer cells during three stages of the cell cycle, as well as those of the endothelial cells that constitute the blood vessel walls. This model is used to qualitatively assess how efficient endostatin gene therapy is. Endostatin is an anti-angiogenic endogenous substance. The gene therapy entails overexpressing endostatin in the tumor and in the surrounding tissue. Simulations show that there is a critical treatment dose below which increasing the duration of treatment leads to a loss of efficacy. This theoretical model may be useful to evaluate the efficacy of therapies targeting angiogenesis, and could therefore contribute to designing prospective clinical trials.
dc.language.isoen
dc.publisherElsevier
dc.subject.enMultiscale mathematical modeling
dc.subject.enCell cycle
dc.subject.enTumor growth
dc.subject.enAngiogenesis
dc.subject.enPharmacological law
dc.subject.enOptimization of cancer treatments
dc.title.enA pharmacologically based multiscale mathematical model of angiogenesis and its use in investigating the efficacy of a new cancer treatment strategy.
dc.typeArticle de revue
dc.identifier.doi10.1016/j.jtbi.2009.06.026
dc.subject.halSciences du Vivant [q-bio]/Cancer
dc.subject.halInformatique [cs]/Modélisation et simulation
bordeaux.journalJournal of Theoretical Biology
bordeaux.page545-62
bordeaux.volume260
bordeaux.issue4
bordeaux.peerReviewedoui
hal.identifierinria-00440447
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//inria-00440447v1
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