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dc.contributor.authorAcar, Aen_US
dc.contributor.authorNichol, Den_US
dc.contributor.authorFernandez-Mateos, Jen_US
dc.contributor.authorCresswell, GDen_US
dc.contributor.authorBarozzi, Ien_US
dc.contributor.authorHong, SPen_US
dc.contributor.authorTrahearn, Nen_US
dc.contributor.authorSpiteri, Ien_US
dc.contributor.authorStubbs, Men_US
dc.contributor.authorBurke, Ren_US
dc.contributor.authorStewart, Aen_US
dc.contributor.authorCaravagna, Gen_US
dc.contributor.authorWerner, Ben_US
dc.contributor.authorVlachogiannis, Gen_US
dc.contributor.authorMaley, CCen_US
dc.contributor.authorMagnani, Len_US
dc.contributor.authorValeri, Nen_US
dc.contributor.authorBanerji, Uen_US
dc.contributor.authorSottoriva, Aen_US
dc.date.accessioned2020-05-26T11:32:12Z
dc.date.issued2020-04-21en_US
dc.identifier.citationNature communications, 2020, 11 (1), pp. 1923 - ?en_US
dc.identifier.issn2041-1723en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3636
dc.identifier.eissn2041-1723en_US
dc.identifier.doi10.1038/s41467-020-15596-zen_US
dc.description.abstractDrug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased fecundity or increased sensitivity to another drug. These evolutionary trade-offs can be exploited using 'evolutionary steering' to control the tumour population and delay resistance. However, recapitulating cancer evolutionary dynamics experimentally remains challenging. Here, we present an approach for evolutionary steering based on a combination of single-cell barcoding, large populations of 10<sup>8</sup>-10<sup>9</sup> cells grown without re-plating, longitudinal non-destructive monitoring of cancer clones, and mathematical modelling of tumour evolution. We demonstrate evolutionary steering in a lung cancer model, showing that it shifts the clonal composition of the tumour in our favour, leading to collateral sensitivity and proliferative costs. Genomic profiling revealed some of the mechanisms that drive evolved sensitivity. This approach allows modelling evolutionary steering strategies that can potentially control treatment resistance.en_US
dc.formatElectronicen_US
dc.format.extent1923 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectHumansen_US
dc.subjectLung Neoplasmsen_US
dc.subjectPyridonesen_US
dc.subjectPyrimidinonesen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectStochastic Processesen_US
dc.subjectComputational Biologyen_US
dc.subjectEvolution, Molecularen_US
dc.subjectDrug Resistance, Neoplasmen_US
dc.subjectGenotypeen_US
dc.subjectModels, Theoreticalen_US
dc.subjectComputer Simulationen_US
dc.subjectClonal Evolutionen_US
dc.subjectMolecular Medicineen_US
dc.subjectGefitiniben_US
dc.titleExploiting evolutionary steering to induce collateral drug sensitivity in cancer.en_US
dc.typeJournal Article
dcterms.dateAccepted2020-03-18en_US
rioxxterms.versionofrecord10.1038/s41467-020-15596-zen_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2020-04-21en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfNature communicationsen_US
pubs.issue1en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Hit Discovery & Structural Design
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Pharmacology – Adaptive Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gastrointestinal Cancer Biology and Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology/Hit Discovery & Structural Design
pubs.publication-statusPublisheden_US
pubs.volume11en_US
pubs.embargo.termsNot knownen_US
icr.researchteamClinical Pharmacology – Adaptive Therapyen_US
icr.researchteamEvolutionary Genomics & Modellingen_US
icr.researchteamGastrointestinal Cancer Biology and Genomicsen_US
icr.researchteamHit Discovery & Structural Designen_US
dc.contributor.icrauthorValeri, Nicolaen_US
dc.contributor.icrauthorBanerji, Udaien_US
dc.contributor.icrauthorSottoriva, Andreaen_US
dc.contributor.icrauthorSpiteri Sagastume, Mariaen_US
dc.contributor.icrauthorBurke, Rosemaryen_US


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