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Nat Clin Pract Oncol. 2008 Jun;5(6):337-47. doi: 10.1038/ncponc1110. Epub 2008 Apr 22.

Mechanisms of Disease: cancer stem cells--targeting the evil twin.

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Genetics and Stem Cell Laboratory, Ecole Polytechnique Fédérale de Lausanne, Swiss Institute for Experimental Cancer Research, School of Life Science, Epalinges, Switzerland.


Classical antineoplastic treatments such as chemotherapy or radiation can efficiently eradicate the majority of proliferating and genetically unstable malignant cells within neoplastic lesions. There is increasing evidence, however, that these regimens frequently fail to eliminate a minor subpopulation of resistant tumor cells that have distinct features of somatic stem cells. These serve as a reservoir for disease recurrence, and are the origin of metastatic growth. These so-called cancer stem cells (CSCs) or cancer-initiating cells represent often a rare, highly self-renewing population within the tumor mass, which is thought to be the only one required for both initiation and maintenance of disease. Tumor-cell populations enriched for CSC activity were originally identified in leukemias, but have now also been uncovered in a number of solid cancers. Their marked resistance towards classical antitumor regimens is mediated by the combination of several critical features, including relative dormancy, efficient DNA repair, high expression of multidrug-resistance-type membrane transporters and protection by a hypoxic niche environment. We review the concept of CSCs with particular emphasis on the mechanism of therapy resistance, and discuss potential future therapeutic interventions with the goal of specifically eliminating CSCs in a clinical setting.

[Indexed for MEDLINE]

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