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World J Gastroenterol. Dec 14, 2006; 12(46): 7440-7450
Published online Dec 14, 2006. doi: 10.3748/wjg.v12.i46.7440
Emerging therapies in gastrointestinal cancers
Jyoti Nautiyal, Arun K Rishi, Adhip PN Majumdar
Jyoti Nautiyal, Karmanos Cancer Institute, Detroit, MI 48201, United States
Arun K Rishi, Adhip PN Majumdar, Karmanos Cancer Institute, Veterans Affairs Medical Center, Departments of Internal Medicine, and, Wayne State University, Detroit, MI 48201, United States
Author contributions: All authors contributed equally to the work.
Supported by grants from the National Institute of Aging (5 RO1 AG14343) (APNM) and the Department of Veterans Affairs (APNM and AKR) and from The Susan G. Komen Foundation for Breast Cancer Research (AKR)
Correspondence to: Adhip PN Majumdar, PhD, DSc. John D. Dingell VA Medical Center, 4646 John R; Room: B-4238, Detroit, MI 48201, United States. a.majumdar@wayne.edu
Telephone: +1-313-5764460 Fax: +1-313-5761112
Received: July 28, 2006
Revised: August 6, 2006
Accepted: August 11, 2006
Published online: December 14, 2006
Abstract

Members of the receptor tyrosine kinase family, that include EGFR, ErbB-2/HER-2, ErbB-3/HER-3 and ErbB-4/HER-4, are frequently implicated in experimental models of epithelial cell neoplasia as well as in human cancers. Therefore, interference with the activation of these growth factor receptors represents a promising strategy for development of novel and selective anticancer therapies. Indeed, a number of inhibitors that target either EGFR or HER-2, with the exception of a few that target both; have been developed for treatment of epithelial cancers. Since most solid tumors express different ErbB receptors and/or their ligands, identification of inhibitor(s), targeting multiple EGFR family members may provide a therapeutic benefit to a broader patient population. Here we describe the significance of an ErbB family of receptors in epithelial cancers, and summarize different available therapeutics targeting these receptors. It also emphasizes the need to develop pan-ErbB inhibitors and discusses EGF-Receptor Related Protein, a recently isolated negative regulator of EGFR as a potential pan-ErbB therapeutic for a wide variety of epithelial cancers.

Keywords: Gastrointestinal cancers; Carcinogenesis; Targeted therapies; Pan-ErbB family; EGF-Receptor Related Protein