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Dose- and time-dependence of the host-mediated response to paclitaxel therapy: a mathematical modeling approach

hal.structure.identifierRappaport faculty of Medicine
dc.contributor.authorBENGUIGUI, Madeleine
hal.structure.identifierRappaport faculty of Medicine
dc.contributor.authorALISHEKEVITZ, Dror
hal.structure.identifierRappaport faculty of Medicine
dc.contributor.authorTIMANER, Michael
hal.structure.identifierRappaport faculty of Medicine
dc.contributor.authorSHECHTER, Dvir
hal.structure.identifierRappaport faculty of Medicine
dc.contributor.authorRAVIV, Ziv
hal.structure.identifierInstitut de Mathématiques de Bordeaux [IMB]
hal.structure.identifierModélisation Mathématique pour l'Oncologie [MONC]
dc.contributor.authorBENZEKRY, Sebastien
hal.structure.identifierRappaport faculty of Medicine
dc.contributor.authorSHAKED, Yuval
dc.date.accessioned2024-04-04T03:07:05Z
dc.date.available2024-04-04T03:07:05Z
dc.date.issued2017-12
dc.identifier.issn1949-2553
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/193401
dc.description.abstractEnIt has recently been suggested that pro-tumorigenic host-mediated processes induced in response to chemotherapy counteract the anti-tumor activity of therapy, and thereby decrease net therapeutic outcome. Here we use experimental data to formulate a mathematical model describing the host response to different doses of paclitaxel (PTX) chemotherapy as well as the duration of the response. Three previously described host-mediated effects are used as readouts for the host response to therapy. These include the levels of circulating endothelial progenitor cells in peripheral blood and the effect of plasma derived from PTX-treated mice on migratory and invasive properties of tumor cells in vitro. A first set of mathematical models, based on basic principles of pharmacokinetics/pharmacodynamics, did not appropriately describe the dose-dependence and duration of the host response regarding the effects on invasion. We therefore provide an alternative mathematical model with a dose-dependent threshold, instead of a concentration-dependent one, that describes better the data. This model is integrated into a global model defining all three host-mediated effects. It not only precisely describes the data, but also correctly predicts host-mediated effects at different doses as well as the duration of the host response. This mathematical model may serve as a tool to predict the host response to chemotherapy in cancer patients, and therefore may be used to design chemotherapy regimens with improved therapeutic outcome by minimizing host mediated effects.
dc.language.isoen
dc.publisherImpact journals
dc.subject.enchemotherapy
dc.subject.enhost effects
dc.subject.enmathematical models
dc.subject.eninvasion and migration
dc.subject.enmetronomic chemotherapy
dc.title.enDose- and time-dependence of the host-mediated response to paclitaxel therapy: a mathematical modeling approach
dc.typeArticle de revue
dc.identifier.doi10.18632/oncotarget.23514
dc.subject.halSciences du Vivant [q-bio]/Cancer
bordeaux.journalOncotarget
bordeaux.page2574-2590
bordeaux.volume9
bordeaux.hal.laboratoriesInstitut de Mathématiques de Bordeaux (IMB) - UMR 5251*
bordeaux.issue2
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionBordeaux INP
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
hal.identifierhal-01672568
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-01672568v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Oncotarget&rft.date=2017-12&rft.volume=9&rft.issue=2&rft.spage=2574-2590&rft.epage=2574-2590&rft.eissn=1949-2553&rft.issn=1949-2553&rft.au=BENGUIGUI,%20Madeleine&ALISHEKEVITZ,%20Dror&TIMANER,%20Michael&SHECHTER,%20Dvir&RAVIV,%20Ziv&rft.genre=article


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