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Table 1 Tenets of the cancer stem cell and clonal evolution models

From: Breast cancer intra-tumor heterogeneity

  Cancer stem cell model Clonal evolution model
Tumorigenic cells CSCs Any cell
Tumor cell organization Hierarchical Stochastic
Capacity of self-renewal with asymmetric divisions CSCs can self-renew indefinitely whereas terminally differentiated cells have limited proliferative potential Not applicable
Progression Driven by CSCs, which account for a small subpopulation of the tumor bulk Driven by the fittest clone under a constellation of selective pressures
Source of heterogeneity Aberrant differentiation program and mutations Epigenetic and genetic aberrations followed by selection
Type of heterogeneity Initially perceived as largely phenotypic; however, more recent studies suggested that CSCs may be genetically heterogeneous within a tumor Genetic and phenotypic heterogeneity
Source of resistance to therapy CSCs Selection of resistant subclones harboring specific genetic or epigenetic aberrations
  1. CSC, cancer stem cell.