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Cancer stem cells with genetic instability: the best vehicle with the best engine for cancer

Gene Therapy volume 15, pages 136–142 (2008)Cite this article

Abstract

Our understanding of the role of stem cells in cancer development is evolving quickly. In the course of tumor expansion, a subpopulation of tumor cells with stem cell-like features has been noted. These cancer stem cells give rise to transit amplifying tumor cells, which comprise the majority of the tumor mass prior to terminal differentiation. Combining this finding with genetic instability, a well-known engine for cancer development and metastases, a new model emerges for cancer where normal stem cells and their cellular pathway acquire stochastic malignant abilities. In this model, when cancer stem cells self-renew, many genetic variants are produced. Just as microbes ‘learn’ to defeat antibiotics, genetically heterogeneous cancer stem cells may possibly acquire resistance to various chemotherapeutic approaches. Drug-resistant microorganisms selected by spontaneous mutation of bacterial DNA may not be so different than the drug-resistant and genetically instable cancer stem cells recurring after chemotherapeutic treatment. In this gloomy view of cancer, cancer stem cells with genetic instability can be considered as ‘the best vehicle with the best engine’, a formidable challenge for the future development of new anticancer therapies.

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Acknowledgements

I am very grateful to Lynda Guzik for editorial assistance. This work was supported in part by the Jeannik M Littlefield-AACR Grant in Metastatic Colon Cancer Research and the Commonwealth of Pennsylvania.

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  1. Department of Pathology, McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA

    E Lagasse

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Lagasse, E. Cancer stem cells with genetic instability: the best vehicle with the best engine for cancer. Gene Ther 15, 136–142 (2008). https://doi.org/10.1038/sj.gt.3303068

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