原创力文档the therapeutic implications of plasticity of the cancer stem cell phenotype治疗癌症干细胞表型可塑性的影响.pdfVIP
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the therapeutic implications of plasticity of the cancer stem cell phenotype治疗癌症干细胞表型可塑性的影响
The Therapeutic Implications of Plasticity of the Cancer
Stem Cell Phenotype
1 2 1
Kevin Leder , Eric C. Holland , Franziska Michor *
1 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, and Department of Biostatistics, Harvard School of Public Health, Boston,
Massachusetts, United States of America, 2 Cancer Biology and Genetics Program, Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, New
York, United States of America
Abstract
The 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 quant
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