ReviewCancer stem cells: Back to Darwin?
Section snippets
Cancer stem cells: now you see them, now you do not
The concept of cancer stem cells (CSCs) has sparked excitement and controversy in equal measure. The arguments touch on fundamental issues of cancer biology but also have potentially critical implications for therapy. The history of the idea has been chronicled elsewhere [1]: suffice to say that the development of the NOD/SCID in vivo assay for human leukaemic stem cells by John Dick and colleagues [2], [3] resurrected a stalled debate and sparked the current explosion of interest.
The concept
The missing link?
A particular anomaly in the cancer stem cell debate is that much of the underlying genetics of cancer tends to be ignored. Cancer development is fundamentally a dynamic, Darwinian process of mutational diversification and clonal selection [25], [26], [27], [28]. In this context, mutant cells with self-renewal or ‘stem’ cells could well be the crucial units of selection. But, in this context, they simply cannot be a fixed entity. They can be anticipated to differ in frequency and in phenotypic
Genetic diversity of cancer stem cells
Recent genome-wide sequencing has revealed that most epithelial carcinomas have extraordinarily complex genetic landscapes in which an undefined number of functionally relevant ‘driver’ mutations lie embedded in a sea of ‘passenger’ mutations or genetic noise [36], [37]. Distilling from this complexity the timing and sequence of critical genetic lesions is an enormous challenge. Also, these genomic portraits are usually presented as if they reflect the singular genotype of the particular cancer
A ‘back to Darwin’ model for cancer propagation
What kind of model of CSC then sits most comfortably with both the genetics and evolutionary biology of cancer? The three ideas preferred (Fig. 1), I suggest, are each inadequate as strict and exclusive alternatives. CSC could, under some circumstances, be developmentally positioned at the apex of a hierarchy but there is no reason to suppose that hierarchical structures are inherently stable and maintained with cancer progression. Some degree of stochastic and seemingly random variation in
Conflict of interest
The author declares that there is no conflict of interest.
Acknowledgements
The author is supported by Leukaemia & Lymphoma Research (UK) and the Kay Kendall Leukaemia Fund (UK).
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