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The Complex Nature of Breast Cancer Stem-Like Cells: Heterogeneity and Plasticity

Rhiannon French and Richard Clarkson

There are multiple definitions of cancer stem cells based on the different assays used to detect or enrich for them. The existence of different assays has made the identification and isolation of the archetypal cancer stem cell (CSC) with all of these properties an attractive but as yet unachievable goal. Indeed, it has been suggested that the lack of complementarity between these assays is in itself a barrier to CSC identification. Yet new insights into the heterogeneity of breast cancer stem cells and the discovery of CSC plasticity now suggests that rather than the existence of a single elusive stem-like entity in cancers, there may be a heterogeneous mix of cell populations able to switch their phenotype under different selective pressures. The aim of this review is to summarise the current evidence supporting this hypothesis and to suggest that focusing on the mechanisms controlling the inter-conversion between these minority stem cell populations could lead to more effective strategies to target the malignant properties of breast cancer stem cells.