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dc.contributor.authorLorenzi, Tommaso
dc.contributor.authorVenkataraman, Chandrasekhar
dc.contributor.authorLorz, Alexander
dc.contributor.authorChaplain, Mark A. J.
dc.date.accessioned2019-05-07T23:37:36Z
dc.date.available2019-05-07T23:37:36Z
dc.date.issued2018-08-14
dc.identifier.citationLorenzi , T , Venkataraman , C , Lorz , A & Chaplain , M A J 2018 , ' The role of spatial variations of abiotic factors in mediating intratumour phenotypic heterogeneity ' , Journal of Theoretical Biology , vol. 451 , pp. 101-110 . https://doi.org/10.1016/j.jtbi.2018.05.002en
dc.identifier.issn0022-5193
dc.identifier.otherPURE: 252985123
dc.identifier.otherPURE UUID: b481322d-6719-49d7-bf85-0bde5937637f
dc.identifier.otherScopus: 85046750884
dc.identifier.otherORCID: /0000-0001-5727-2160/work/55378933
dc.identifier.otherWOS: 000434002000010
dc.identifier.urihttp://hdl.handle.net/10023/17662
dc.descriptionCV wishes to acknowledge partial support from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 642866. AL was supported by King Abdullah University of Science and Technology (KAUST) baseline and start-up funds (BAS/1/1648-01-01 and BAS/1/1648-01-02). MAJC gratefully acknowledge support of EPSRC grant no. EP/N014642/1.en
dc.description.abstractWe present here a space- and phenotype-structured model of selection dynamics between cancer cells within a solid tumour. In the framework of this model, we combine formal analyses with numerical simulations to investigate in silico the role played by the spatial distribution of abiotic components of the tumour microenvironment in mediating phenotypic selection of cancer cells. Numerical simulations are performed both on the 3D geometry of an in silico multicellular tumour spheroid and on the 3D geometry of an in vivo human hepatic tumour, which was imaged using computerised tomography. The results obtained show that inhomogeneities in the spatial distribution of oxygen, currently observed in solid tumours, can promote the creation of distinct local niches and lead to the selection of different phenotypic variants within the same tumour. This process fosters the emergence of stable phenotypic heterogeneity and supports the presence of hypoxic cells resistant to cytotoxic therapy prior to treatment. Our theoretical results demonstrate the importance of integrating spatial data with ecological principles when evaluating the therapeutic response of solid tumours to cytotoxic therapy.
dc.language.isoeng
dc.relation.ispartofJournal of Theoretical Biologyen
dc.rights© 2018 Elsevier Ltd. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version 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/10.1016/j.jtbi.2018.05.002en
dc.subjectIntratumour heterogeneityen
dc.subjectPhenotypic selectionen
dc.subjectMathematical oncologyen
dc.subjectPartial differential equationsen
dc.subjectFinite element methodsen
dc.subjectHA Statisticsen
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectQA Mathematicsen
dc.subjectDASen
dc.subject.lccHAen
dc.subject.lccRC0254en
dc.subject.lccQAen
dc.titleThe role of spatial variations of abiotic factors in mediating intratumour phenotypic heterogeneityen
dc.typeJournal articleen
dc.description.versionPostprinten
dc.contributor.institutionUniversity of St Andrews.Applied Mathematicsen
dc.identifier.doihttps://doi.org/10.1016/j.jtbi.2018.05.002
dc.description.statusPeer revieweden
dc.date.embargoedUntil2019-05-08


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