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Cell Stem Cell. 2014 Dec 4;15(6):692-705. doi: 10.1016/j.stem.2014.11.012.

Colorectal cancer stem cells: from the crypt to the clinic.

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Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Electronic address:
Department of Surgical and Oncological Sciences, Via del Vespro 131, University of Palermo, 90127 Palermo, Italy.
Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy. Electronic address:


Since their first discovery, investigations of colorectal cancer stem cells (CSCs) have revealed some unexpected properties, including a high degree of heterogeneity and plasticity. By exploiting a combination of genetic, epigenetic, and microenvironmental factors, colorectal CSCs metastasize, resist chemotherapy, and continually adapt to a changing microenvironment, representing a formidable challenge to cancer eradication. Here, we review the current understanding of colorectal CSCs, including their origin, relationship to stem cells of the intestine, phenotypic characterization, and underlying regulatory mechanisms. We also discuss limitations to current preclinical models of colorectal cancer and how understanding CSC plasticity can improve the development of clinical strategies.

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