EMT, CSCs, and drug resistance: the mechanistic link and clinical implications
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Author(s)
Shibue, Tsukasa
Weinberg, Robert A
Date Issued
April 2017
Journal
Nature Reviews Clinical Oncology
Publisher
Nature Publishing Group
Citation
Shibue, Tsukasa and Robert A. Weinberg. “EMT, CSCs, and Drug Resistance: The Mechanistic Link and Clinical Implications.” Nature Reviews Clinical Oncology 14, 10 (April 2017): 611–629 © 2017 Macmillan Publishers Limited, part of Springer Nature
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Author's final manuscript
Abstract
The success of anticancer therapy is usually limited by the development of drug resistance. Such acquired resistance is driven, in part, by intratumoural heterogeneity-that is, the phenotypic diversity of cancer cells co-inhabiting a single tumour mass. The introduction of the cancer stem cell (CSC) concept, which posits the presence of minor subpopulations of CSCs that are uniquely capable of seeding new tumours, has provided a framework for understanding one dimension of intratumoural heterogeneity. This concept, taken together with the identification of the epithelial-to-mesenchymal transition (EMT) programme as a critical regulator of the CSC phenotype, offers an opportunity to investigate the nature of intratumoural heterogeneity and a possible mechanistic basis for anticancer drug resistance. In fact, accumulating evidence indicates that conventional therapies often fail to eradicate carcinoma cells that have entered the CSC state via activation of the EMT programme, thereby permitting CSC-mediated clinical relapse. In this Review, we summarize our current understanding of the link between the EMT programme and the CSC state, and also discuss how this knowledge can contribute to improvements in clinical practice.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1038/NRCLINONC.2017.44
