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dc.contributor.authorLeder, Kevin
dc.contributor.authorHolland, Eric C.
dc.contributor.authorMichor, Franziska L.
dc.date.accessioned2012-04-24T13:40:52Z
dc.date.issued2010
dc.identifier.citationLeder, Kevin, Eric C. Holland, and Franziska Michor. 2010. The Therapeutic Implications of Plasticity of the Cancer Stem Cell Phenotype. PLoS ONE 5(12): e14366.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:8607106
dc.description.abstractThe cancer stem cell hypothesis suggests that tumors contain a small population of cancer cells that have the ability to undergo symmetric self-renewing cell division. In tumors that follow this model, cancer stem cells produce various kinds of specified precursors that divide a limited number of times before terminally differentiating or undergoing apoptosis. As cells within the tumor mature, they become progressively more restricted in the cell types to which they can give rise. However, in some tumor types, the presence of certain extra- or intracellular signals can induce committed cancer progenitors to revert to a multipotential cancer stem cell state. In this paper, we design a novel mathematical model to investigate the dynamics of tumor progression in such situations, and study the implications of a reversible cancer stem cell phenotype for therapeutic interventions. We find that higher levels of dedifferentiation substantially reduce the effectiveness of therapy directed at cancer stem cells by leading to higher rates of resistance. We conclude that plasticity of the cancer stem cell phenotype is an important determinant of the prognosis of tumors. This model represents the first mathematical investigation of this tumor trait and contributes to a quantitative understanding of cancer.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0014366en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003707/pdf/en_US
dash.licenseLAA
dc.subjectcell biologyen_US
dc.subjectoncologyen_US
dc.subjectcomputational biology/evolutionary modelingen_US
dc.subjectcomputational biology/systems biologyen_US
dc.titleThe Therapeutic Implications of Plasticity of the Cancer Stem Cell Phenotypeen_US
dc.typeJournal Articleen_US
dc.description.versionAuthor's Originalen_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorMichor, Franziska L.
dc.date.available2012-04-24T13:40:52Z
dash.affiliation.otherSPH^Biostatisticsen_US
dash.affiliation.otherSPH^Biostatisticsen_US
dc.identifier.doi10.1371/journal.pone.0014366*
dash.contributor.affiliatedLeder, Kevin
dash.contributor.affiliatedMichor, Franziska


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