Topic Highlight
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2015; 21(43): 12261-12273
Published online Nov 21, 2015. doi: 10.3748/wjg.v21.i43.12261
Targeting the PI3K/Akt signaling pathway in gastric carcinoma: A reality for personalized medicine?
Shikha Satendra Singh, Wei Ney Yap, Frank Arfuso, Shreya Kar, Chao Wang, Wanpei Cai, Arunasalam M Dharmarajan, Gautam Sethi, Alan Prem Kumar
Shikha Satendra Singh, Wei Ney Yap, Shreya Kar, Chao Wang, Wanpei Cai, Gautam Sethi, Alan Prem Kumar, Cancer Science Institute of Singapore, National University of Singapore, Singapore City 117597, Singapore
Shikha Satendra Singh, Wei Ney Yap, Shreya Kar, Chao Wang, Wanpei Cai, Gautam Sethi, Alan Prem Kumar, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City 117597, Singapore
Wei Ney Yap, Davos Life Science Pte Ltd, Singapore City 138667, Singapore
Frank Arfuso, Arunasalam M Dharmarajan, Gautam Sethi, Alan Prem Kumar, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia 6102, Australia
Alan Prem Kumar, National University Cancer Institute, Singapore City 119074, Singapore
Alan Prem Kumar, Department of Biological Sciences, University of North Texas, Denton, TX 76203-5017, United States
Author contributions: Singh SS, Yap WN, Arfuso F, Kar S, Wang C, Cai W did the research and wrote the draft review paper; Dharmarajan MA, Sethi G and Kumar AP did all the editing and inclusion of additional information for the final review paper.
Supported by National Medical Research Council IRG and NUHS Bench-to-Bedside grants (to Sethi G); grants from the National Medical Research Council of Singapore (R-713-000-177-511); the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiative to Cancer Science Institute of Singapore; National University of Singapore and by the NCIS Yong Siew Yoon Research Grant through donations from the Yong Loo Lin Trust (to Kumar AP).
Conflict-of-interest statement: The authors have no conflict of interest to report.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Dr. Alan Prem Kumar, PhD, Cancer Science Institute of Singapore, National University of Singapore, Singapore City 117597, Singapore.
Telephone: +65-65165456 Fax: +65-68739664
Received: May 26, 2015
Peer-review started: May 28, 2015
First decision: July 14, 2015
Revised: August 12, 2015
Accepted: October 23, 2015
Article in press: October 26, 2015
Published online: November 21, 2015

Frequent activation of phosphatidylinositol-3 kinases (PI3K)/Akt/mTOR signaling pathway in gastric cancer (GC) is gaining immense popularity with identification of mutations and/or amplifications of PIK3CA gene or loss of function of PTEN, a tumor suppressor protein, to name a few; both playing a crucial role in regulating this pathway. These aberrations result in dysregulation of this pathway eventually leading to gastric oncogenesis, hence, there is a need for targeted therapy for more effective anticancer treatment. Several inhibitors are currently in either preclinical or clinical stages for treatment of solid tumors like GC. With so many inhibitors under development, further studies on predictive biomarkers are needed to measure the specificity of any therapeutic intervention. Herein, we review the common dysregulation of PI3K/Akt/mTOR pathway in GC and the various types of single or dual pathway inhibitors under development that might have a superior role in GC treatment. We also summarize the recent developments in identification of predictive biomarkers and propose use of predictive biomarkers to facilitate more personalized cancer therapy with effective PI3K/Akt/mTOR pathway inhibition.

Keywords: Epidemiology, Gastric cancer, PI3K/Akt/mTOR pathway, Predictive biomarkers, Targeted therapy

Core tip: Gastric cancer (GC) is the fifth most common cancer in the world with highest incidence rate in Eastern Asia and Latin America. With increase in GC patient relapse and drug resistance, targeted therapy is gaining immense popularity for GC treatment. One of the pathways which has been reported to be dysregulated is phosphatidylinositol-3 kinases (PI3K)/Akt signaling pathway. This review focuses on how this pathway is crucial in GC oncogenesis. We also summarize the single or dual PI3K/Akt pathway inhibitors under investigation for GC treatment. Thereby, we discuss the plausible novel biomarkers under investigation for a more tailored approach for GC treatment.