Catching moving targets: cancer stem cell hierarchies, therapy-resistance & considerations for clinical intervention.
Issue Date
2017MeSH
Antineoplastic AgentsCell Differentiation
Drug Resistance, Neoplasm
Humans
Neoplasms
Neoplastic Stem Cells
Signal Transduction
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Catching moving targets: cancer stem cell hierarchies, therapy-resistance & considerations for clinical intervention. 2017, 16 (1):43 Mol. CancerPublisher
BioMed CentralJournal
Molecular cancerDOI
10.1186/s12943-017-0601-3PubMed ID
28228161Abstract
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.Item Type
ArticleLanguage
enISSN
1476-4598ae974a485f413a2113503eed53cd6c53
10.1186/s12943-017-0601-3
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