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Catching moving targets: cancer stem cell hierarchies, therapy-resistance & considerations for clinical intervention.

Catching moving targets: cancer stem cell hierarchies, therapy-resistance & considerations for clinical intervention.
Author Information (click to view)

Gasch C, Ffrench B, O'Leary JJ, Gallagher MF,


Gasch C, Ffrench B, O'Leary JJ, Gallagher MF, (click to view)

Gasch C, Ffrench B, O'Leary JJ, Gallagher MF,

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Molecular cancer 2017 02 2316(1) 43 doi 10.1186/s12943-017-0601-3
Abstract

It is widely believed that targeting the tumour-initiating cancer stem cell (CSC) component of malignancy has great therapeutic potential, particularly in therapy-resistant disease. However, despite concerted efforts, CSC-targeting strategies have not been efficiently translated to the clinic. This is partly due to our incomplete understanding of the mechanisms underlying CSC therapy-resistance. In particular, the relationship between therapy-resistance and the organisation of CSCs as Stem-Progenitor-Differentiated cell hierarchies has not been widely studied. In this review we argue that modern clinical strategies should appreciate that the CSC hierarchy is a dynamic target that contains sensitive and resistant components and expresses a collection of therapy-resisting mechanisms. We propose that the CSC hierarchy at primary presentation changes in response to clinical intervention, resulting in a recurrent malignancy that should be targeted differently. As such, addressing the hierarchical organisation of CSCs into our bench-side theory should expedite translation of CSC-targeting to bed-side practice. In conclusion, we discuss strategies through which we can catch these moving clinical targets to specifically compromise therapy-resistant disease.

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