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World J Stem Cells. Nov 26, 2014; 6(5): 606-613
Published online Nov 26, 2014. doi: 10.4252/wjsc.v6.i5.606
Stem cells in gastrointestinal cancers: The road less travelled
Sameh Mikhail, Amer Zeidan
Sameh Mikhail, the Ohio State University, Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, United States
Amer Zeidan, Yale Comprehensive Cancer Center, Section of Hematology, Department of Internal Medicine, Yale University, New Haven, CT 06520-8028, United States
Author contributions: Mikhail S and Zeidan A contributed to this paper.
Correspondence to: Amer Zeidan, MBBS, MhS, Yale Comprehensive Cancer Center, Section of Hematology, Department of Internal Medicine, Yale University, 333 Cedar street, PO. Box 208028, New Haven, CT 06520-8028, United States. amer.zeidan@yale.edu
Telephone: +1-203-7377103 Fax: +1-203-7857232
Received: July 25, 2014
Revised: August 29, 2014
Accepted: September 6, 2014
Published online: November 26, 2014
Processing time: 65 Days and 5.4 Hours
Abstract

Cancer stem cells (CSC) are thought to be malignant cells that have the capacity to initiate and maintain tumor growth and survival. Studies have described CSC in various gastrointestinal neoplasms such as colon, pancreas and liver and gastroesophageal tumors. The mechanism by which CSC develop remains unclear. Several studies have explored the role of dysregulation of the Wnt/β-catenin, transformation growth factor-beta and hedhog pathways in generation of CSC. In this review, we discuss the various molecular abnormalities that may be related to formation of CSC in gastrointestinal malignancies, strategies to identify CSC and therapeutic strategies that are based on these concepts. Identification and targeting CSC is an intriguing area and may provide a new therapeutic option for patients with cancer including gastrointestinal malignancies. Although great progress has been made, many issues need to be addressed. Precise targeting of CSC will require precise isolation and characterization of those cells. This field is also evolving but further research is needed to identify markers that are specific for CSC. Although the application of this field has not entered the clinic yet, there continues to be significant optimism about its potential utility in overcoming cancer resistance and curing patients with cancer.

Keywords: Cancer stem cells; CD133+; WNT/β-catenin; Transformation growth factor-beta; Hedgehog; Notch

Core tip: Cancer stem cells (CSC) are thought to be malignant cells that have the capacity to initiate and maintain tumor growth and survival. Several studies have explored the role of dysregulation of the Wnt/β- catenin, transformation growth factor-beta and hedhog pathways in generation of CSC. The exact machismo of their development, however, remains unknown. Several investigators have researched modalities to identify and target CSC. In this review, we summarize the recent evidence exploring the mechanisms of development, identification and targeting of CSC in gastrointestinal malignancies.