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dc.contributor.authorStace, Rebecca E. A.
dc.contributor.authorStiehl, Thomas
dc.contributor.authorChaplain, Mark A. J.
dc.contributor.authorMarciniak-Czochra, Anna
dc.contributor.authorLorenzi, Tommaso
dc.date.accessioned2020-03-25T16:30:01Z
dc.date.available2020-03-25T16:30:01Z
dc.date.issued2020
dc.identifier.citationStace , R E A , Stiehl , T , Chaplain , M A J , Marciniak-Czochra , A & Lorenzi , T 2020 , ' Discrete and continuum phenotype-structured models for the evolution of cancer cell populations under chemotherapy ' , Mathematical Modelling of Natural Phenomena , vol. 15 , 14 . https://doi.org/10.1051/mmnp/2019027en
dc.identifier.issn0973-5348
dc.identifier.otherPURE: 259389522
dc.identifier.otherPURE UUID: 5966d364-10fb-4ce2-8d89-794934d97897
dc.identifier.otherORCID: /0000-0001-5727-2160/work/71221596
dc.identifier.urihttp://hdl.handle.net/10023/19709
dc.descriptionFunding: German Research Foundation DFG (SFB 873; subproject B08) (T.S. and A.M.-C); Heidelberg Graduate School (T.L.).en
dc.description.abstractWe present a stochastic individual-based model for the phenotypic evolution of cancer cell populations under chemotherapy. In particular, we consider the case of combination cancer therapy whereby a chemotherapeutic agent is administered as the primary treatment and an epigenetic drug is used as an adjuvant treatment. The cell population is structured by the expression level of a gene that controls cell proliferation and chemoresistance. In order to obtain an analytical description of evolutionary dynamics, we formally derive a deterministic continuum counterpart of this discrete model, which is given by a nonlocal parabolic equation for the cell population density function. Integrating computational simulations of the individual-based model with analysis of the corresponding continuum model, we perform a complete exploration of the model parameter space. We show that harsher environmental conditions and higher probabilities of spontaneous epimutation can lead to more effective chemotherapy, and we demonstrate the existence of an inverse relationship between the efficacy of the epigenetic drug and the probability of spontaneous epimutation. Taken together, the outcomes of the model provide theoretical ground for the development of anticancer protocols that use lower concentrations of chemotherapeutic agents in combination with epigenetic drugs capable of promoting the re-expression of epigenetically regulated genes.
dc.format.extent22
dc.language.isoeng
dc.relation.ispartofMathematical Modelling of Natural Phenomenaen
dc.rightsCopyright © 2020 EDP Sciences. This work has been made available online in accordance with publisher policies or with permission. Permission for further reuse of this content should be sought from the publisher or the rights holder. This is the author created accepted manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1051/mmnp/2019027en
dc.subjectCancer cell populationsen
dc.subjectChemotherapyen
dc.subjectEpigenetic drugsen
dc.subjectIndividual-based modelsen
dc.subjectNonlocal parabolic equationsen
dc.subjectQA Mathematicsen
dc.subjectQH301 Biologyen
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectRM Therapeutics. Pharmacologyen
dc.subjectEen
dc.subject.lccQAen
dc.subject.lccQH301en
dc.subject.lccRC0254en
dc.subject.lccRMen
dc.titleDiscrete and continuum phenotype-structured models for the evolution of cancer cell populations under chemotherapyen
dc.typeJournal articleen
dc.description.versionPostprinten
dc.contributor.institutionUniversity of St Andrews.School of Mathematics and Statisticsen
dc.contributor.institutionUniversity of St Andrews.Applied Mathematicsen
dc.identifier.doihttps://doi.org/10.1051/mmnp/2019027
dc.description.statusPeer revieweden
dc.date.embargoedUntil2020-03-12


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