Show simple item record

hal.structure.identifierH. Lee Moffitt Cancer Center & Research Institute
dc.contributor.authorCunningham, Jessica
hal.structure.identifierMaastricht University [Maastricht]
dc.contributor.authorThuijsman, Frank
hal.structure.identifierDept. Mathematics [Maastricht]
dc.contributor.authorPeeters, Ralf
hal.structure.identifierCEntre de REcherches en MAthématiques de la DEcision [CEREMADE]
dc.contributor.authorViossat, Yannick
hal.structure.identifierH. Lee Moffitt Cancer Center & Research Institute
dc.contributor.authorBrown, Joel
hal.structure.identifierH. Lee Moffitt Cancer Center & Research Institute
dc.contributor.authorGatenby, Robert
hal.structure.identifierMaastricht University [Maastricht]
dc.contributor.authorStaňková, K.
dc.date.accessioned2021-11-24T15:22:51Z
dc.date.available2021-11-24T15:22:51Z
dc.date.issued2020
dc.identifier.issn1932-6203
dc.identifier.urihttps://basepub.dauphine.psl.eu/handle/123456789/22238
dc.language.isoenen
dc.subjectcancer treatmenten
dc.subjectprostate canceren
dc.subjectbreast canceren
dc.subjectmetastasisen
dc.subjectsystem stabilityen
dc.subject.ddc515en
dc.titleOptimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate canceren
dc.typeArticle accepté pour publication ou publié
dc.description.abstractenIn the absence of curative therapies, treatment of metastatic castrate-resistant prostate cancer (mCRPC) using currently available drugs can be improved by integrating evolutionary principles that govern proliferation of resistant subpopulations into current treatment protocols. Here we develop what is coined as an ‘evolutionary stable therapy’, within the context of the mathematical model that has been used to inform the first adaptive therapy clinical trial of mCRPC. The objective of this therapy is to maintain a stable polymorphic tumor heterogeneity of sensitive and resistant cells to therapy in order to prolong treatment efficacy and progression free survival. Optimal control analysis shows that an increasing dose titration protocol, a very common clinical dosing process, can achieve tumor stabilization for a wide range of potential initial tumor compositions and volumes. Furthermore, larger tumor volumes may counter intuitively be more likely to be stabilized if sensitive cells dominate the tumor composition at time of initial treatment, suggesting a delay of initial treatment could prove beneficial. While it remains uncertain if metastatic disease in humans has the properties that allow it to be truly stabilized, the benefits of a dose titration protocol warrant additional pre-clinical and clinical investigations.en
dc.relation.isversionofjnlnamePLoS ONE
dc.relation.isversionofjnlvol15en
dc.relation.isversionofjnlissue12en
dc.relation.isversionofjnldate2020-12
dc.relation.isversionofdoi10.1371/journal.pone.0243386en
dc.relation.isversionofjnlpublisherPublic Library of Scienceen
dc.subject.ddclabelAnalyseen
dc.relation.forthcomingnonen
dc.description.ssrncandidatenon
dc.description.halcandidatenonen
dc.description.readershiprechercheen
dc.description.audienceInternationalen
dc.relation.Isversionofjnlpeerreviewedouien
dc.date.updated2021-11-24T15:17:22Z
hal.author.functionaut
hal.author.functionaut
hal.author.functionaut
hal.author.functionaut
hal.author.functionaut
hal.author.functionaut
hal.author.functionaut


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record