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Identification and targeting of cancer stem cells
Authors:Tobias Schatton  Natasha Y. Frank  Markus H. Frank
Affiliation:1. Transplantation Research Center, Children's Hospital Boston & Brigham and Women's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA;2. Department of Medicine, VA Boston Healthcare System, 1400 VFW Parkway, West Roxbury, MA 02132, USA;3. Division of Genetics, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston, MA 02115, USA;4. Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
Abstract:Cancer stem cells (CSC) represent malignant cell subsets in hierarchically organized tumors, which are selectively capable of tumor initiation and self‐renewal and give rise to bulk populations of non‐tumorigenic cancer cell progeny through differentiation. Robust evidence for the existence of prospectively identifiable CSC among cancer bulk populations has been generated using marker‐specific genetic lineage tracking of molecularly defined cancer subpopulations in competitive tumor development models. Moreover, novel mechanisms and relationships have been discovered that link CSC to cancer therapeutic resistance and clinical tumor progression. Importantly, proof‐of‐principle for the potential therapeutic utility of the CSC concept has recently been provided by demonstrating that selective killing of CSC through a prospective molecular marker can inhibit tumor growth. Herein, we review these novel and translationally relevant research developments and discuss potential strategies for CSC‐targeted therapy in the context of resistance mechanisms and molecular pathways preferentially operative in CSC.
Keywords:ABCB5  cancer stem cells  genetic lineage tracking  melanoma  tumor hierarchy
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