title: Cancer stem cells: back to Darwin?
abstract: Current models of cancer propagation or 'stem' cells pay scant attention to the evolutionary dynamics of cancer or to the underlying genetic, mutational drivers. Recent genetic studies on acute lymphoblastic leukaemia at the single cell level reveal a complex non-linear, branching clonal architecture-with sub-clones having distinctive genetic signatures. Most cancers appropriately interrogated are found to have intra-clonal genetic heterogeneity indicative of divergent clonal evolution. These data further suggest that clonal architecture might be driven by genetic heterogeneity of propagating or 'stem' cells. When assayed for leukaemic regeneration in NOD/SCID/gamma mice, genetically diverse 'stem' cells read-out, broadly reflecting the clonal architecture. This has suggested a 'back to Darwin' model for cancer propagation. In this, cells with self-renewal potency or 'stem-ness' provide genetically diverse units of evolutionary selection in cancer progression. The model has significant implications for targeted cancer therapy.
authors.affiliation: Section of Haemato-Oncology, The Institute of Cancer Research, Brookes Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom. mel.greaves@icr.ac.uk <mel.greaves@icr.ac.uk>
authors.forename: Mel
authors.initials: M
authors.lastname: Greaves
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*