Published online Nov 21, 2015. doi: 10.3748/wjg.v21.i43.12261
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.
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.