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Nat Rev Drug Discov. 2014 Jul;13(7):497-512. doi: 10.1038/nrd4253.

Tackling the cancer stem cells - what challenges do they pose?

Author information

1
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
2
1] Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA. [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA; and the MIT Ludwig Center for Molecular Oncology, Cambridge, Massachusetts 02139, USA.

Abstract

Since their identification in 1994, cancer stem cells (CSCs) have been objects of intensive study. Their properties and mechanisms of formation have become a major focus of current cancer research, in part because of their enhanced ability to initiate and drive tumour growth and their intrinsic resistance to conventional therapeutics. The discovery that activation of the epithelial-to-mesenchymal transition (EMT) programme in carcinoma cells can give rise to cells with stem-like properties has provided one possible mechanism explaining how CSCs arise and presents a possible avenue for their therapeutic manipulation. Here we address recent developments in CSC research, focusing on carcinomas that are able to undergo EMT. We discuss the signalling pathways that create these cells, cell-intrinsic mechanisms that could be exploited for selective elimination or induction of their differentiation, and the role of the tumour microenvironment in sustaining them. Finally, we propose ways to use our current knowledge of the complex biology of CSCs to design novel therapies to eliminate them.

PMID:
24981363
PMCID:
PMC4234172
DOI:
10.1038/nrd4253
[Indexed for MEDLINE]
Free PMC Article

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