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World J Clin Oncol. Mar 10, 2011; 2(3): 135-149
Published online Mar 10, 2011. doi: 10.5306/wjco.v2.i3.135
Targeting metastatic upper gastrointestinal adenocarcinomas
Jennifer L Spratlin, Quincy Chu, Sheryl Koski, Karen King, Karen Mulder
Jennifer L Spratlin, Quincy Chu, Sheryl Koski, Karen King, Karen Mulder, Cross Cancer Institute, University of Alberta, T6G 1Z2, Edmonton, Alberta, Canada
Author contributions: All authors contributed to the writing and development of this manuscript; Spratlin JL and Mulder K were responsible for preparing the final version of the manuscript; all authors have read and agree with the final version of the manuscript.
Correspondence to: Jennifer L Spratlin, MD, FRCPC, Assistant Professor, Medical Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, AB, T6G 1Z2, Edmonton, Alberta, Canada. jennifer.spratlin@albertahealthservices.ca
Telephone: +1-780-4328513 Fax: +1-780-4328888
Received: August 19, 2010
Revised: November 20, 2010
Accepted: November 27, 2010
Published online: March 10, 2011

Upper gastrointestinal (GI) tumors, including adenocarcinoma of the esophagus, stomach, pancreas, and biliary tree, have traditionally been difficult to treat with cytotoxic chemotherapeutic agents. There has been little drug development success in treating these cancers over the last 20 years, perhaps a reflection of a combination of the aggressive biology of these tumors, the void in effective and specific drug development for these varied tumors, and the lack of properly designed, biologically-based clinical trials. Recently, so called “targeted agents” have risen to the forefront in the care of cancer patients and have made strong impacts in many areas of oncology, particularly gastrointestinal stromal tumors (GIST), colon, breast, and lung cancers. Unfortunately, slow progress has been made using such agents in upper GI tumors. However, more recently, trials in some tumor types have demonstrated gains in progression free survival and overall survival. In this review, we discuss the drugs and pathways that have been most successful in the treatment of upper GI tumors and present the relevant data supporting their use for each tumor site. Additionally, we will explore a few novel pathways that may prove effective in the treatment of upper GI malignancies in the near future.

Keywords: Targeted therapy, Epidermal growth factor inhibition, Angiogenesis, Antiangiogenic agents, Mammalian target of rapamycin, Her2/neu, Tyrosine kinase inhibition, Pancreatic cancer, Gastric cancer, Biliary cancer, Hepatocellular cancer