Introduction Many tissues in the human body undergo rapid and continuous cell turnover. Maintenance of homeostasis via apoptosis and tissue renewal is a tightly regulated process, orchestrated by a small minority of undifferentiated cells that are quite different than their short-lived relatives. These differences that characterize stem cells comprise 3 defining properties: the ability for self-renewal, the capacity to gen- erate mature tissue through differentiation, and the ability for homeostatic control. 1 Three different groups of stem cells exist: embryonic, ger- minal, and somatic stem cells. 2 Embryonic stem cells (ESCs), originating during blastocysts development, are regarded as the ancestors of all the different cells of a developed organism and are therefore characterized as pluripotent. During physi- ologic embryogenesis, offspring of embryonic stem cells lose their pluripotent potential. Germinal stem cells generate eggs and sperm and are responsible for sexual reproduction. In contrast, somatic stem cells (SSCs) are more limited in their potency because they produce cells that differentiate into mature functioning cells. This restricted potency, termed multipotency, results in production of only a closely related family of cells. Embryonic stem cells and SSCs differ not only with respect to their potency (ie, pluripotent vs. multipotent) but also in their mechanism of cell division. Embryonic stem cells tend to divide symmetrically into 2 equally large daughter cells, whereas tissue stem cells generally divide asymmetrically with one cell retaining stem cell features while the other daughter cell is committed to differentiation. The later cells are commonly known as transient-amplifying (TA) cells in several tissues or as progenitor cells in hematopoietic tis- sues. Transient-amplifying cells are of critical importance for cell proliferation, cell differentiation, and physiologic tissue renewal. Somatic stem cells, or adult stem cells, regulate tissue renewal in organs like the intestine or the hematopoietic system; therefore, they are of major interest in the field of cancer biology. We will provide an update of the biologic basis of the cancer stem cell (CSC) model and possible targets in colon cancer. Cancer Stem Cells The concept that cancer might arise from a rare popula- tion of cells with stem cell–like properties was proposed 150 years ago. 3,4 Increasing evidence over the past 2 decades suggests the existence of a small subgroup of cells Alexandra Pohl, 1 Georg Lurje, 1 Michael Kahn, 2 Heinz-Josef Lenz 1 Abstract Submitted: Nov 2, 2007; Revised: Dec 8, 2007; Accepted: Dec 17, 2007 Review Comprehensive Clinical Colorectal Cancer, Vol. 7, No. 2, 92-98, 2008 Key words: β-Catenin, Stem cell niche, Transient-amplifying cells, Wnt signaling pathway Address for correspondence: Heinz-Josef Lenz, MD, Division of Medical Oncology, University of Southern California, Norris Comprehensive Cancer Center, Keck School of Medicine, 1441 Eastlake Ave, Los Angeles, CA 90033 Fax: 323-865-0061; e-mail: lenz@usc.edu Stem Cells in Colon Cancer 1 Division of Medical Oncology, University of Southern California, Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles 2 Center for Stem Cell and Regenerative Medicine, University of Southern California, Zilkha Neurogenetics Institute, Keck School of Medicine, Los Angeles The concept that cancer might arise from a rare population of cells with stem cell–like properties was proposed 150 years ago. Increasing evidence during the past 2 decades suggests the existence of a small subgroup of cells in cancer that are responsible for tumor growth and proliferation. Stem cells have self- renewing properties; thus, they are appealing candidates for generating the malignant phenotype. Although the concept of stem cells in leukemia has received significant attention for more than the past decade, over the past several years, expression of several surface markers on cancer cells has led to identification of tumor-initiating cells in several solid tumors, including melanoma, brain, breast, prostate, liver, pancreatic, ovarian, and recently, colon cancer. This review will provide an update of the biologic basis of the stem cell model and possible targets for the treatment of colon cancer. Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by CIG Media Group, LP, ISSN #1533-0028, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400. 92 • Clinical Colorectal Cancer March 2008