Targeting the PI3K/Akt signaling pathway in gastric carcinoma: A reality for personalized medicine?

Frequent activation of phosphatidylinositol-3 kinases(PI3K)/Akt/m TOR signaling pathway in gastric cancer(GC) is gaining immense popularity with identification of mutations and/or amplifications of PIK3 CA gene or loss of function of PTEN,a tumor suppressor protein,to name a few; both playing a cruc...

Full description

Saved in:
Bibliographic Details
Published inWorld journal of gastroenterology : WJG Vol. 21; no. 43; pp. 12261 - 12273
Main Author Singh, Shikha Satendra
Format Journal Article
LanguageEnglish
Published United States Baishideng Publishing Group Inc 21.11.2015
Subjects
Animals
Antineoplastic Agents - therapeutic use
Biomarkers, Tumor - antagonists & inhibitors
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
cancer;PI3K/Akt
Carcinoma - drug therapy
Carcinoma - enzymology
Carcinoma - genetics
Carcinoma - pathology
Drug Discovery - methods
Epidemiology;Gastric
Humans
Molecular Targeted Therapy
pathwa
Phosphatidylinositol 3-Kinase - antagonists & inhibitors
Phosphatidylinositol 3-Kinase - genetics
Phosphatidylinositol 3-Kinase - metabolism
Precision Medicine
Protein Kinase Inhibitors - therapeutic use
Proto-Oncogene Proteins c-akt - antagonists & inhibitors
Proto-Oncogene Proteins c-akt - genetics
Proto-Oncogene Proteins c-akt - metabolism
Signal Transduction - drug effects
Stomach Neoplasms - drug therapy
Stomach Neoplasms - enzymology
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
Topic Highlight
TOR
TOR Serine-Threonine Kinases - antagonists & inhibitors
TOR Serine-Threonine Kinases - metabolism
Treatment Outcome
Targeted therapy
Epidemiology
Gastric cancer
PI3K/Akt/mTOR pathway
Predictive biomarkers
Online AccessGet full text

Cover

More Information
Summary:Frequent activation of phosphatidylinositol-3 kinases(PI3K)/Akt/m TOR signaling pathway in gastric cancer(GC) is gaining immense popularity with identification of mutations and/or amplifications of PIK3 CA 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/m TOR 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/m TOR pathway inhibition.
Bibliography:Epidemiology;Gastric cancer;PI3K/Akt/ m TOR pathwa
Frequent activation of phosphatidylinositol-3 kinases(PI3K)/Akt/m TOR signaling pathway in gastric cancer(GC) is gaining immense popularity with identification of mutations and/or amplifications of PIK3 CA 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/m TOR 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/m TOR pathway inhibition.
Shikha Satendra Singh;Wei Ney Yap;Frank Arfuso;Shreya Kar;Chao Wang;Wanpei Cai;Arunasalam M Dharmarajan;Gautam Sethi;Alan Prem Kumar;Cancer Science Institute of Singapore,National University of Singapore;Department of Pharmacology,Yong Loo Lin School of Medicine,National University of Singapore;Davos Life Science Pte Ltd;School of Biomedical Sciences,Curtin Health Innovation Research Institute,Curtin University;National University Cancer Institute;Department of Biological Sciences,University of North Texas
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
ObjectType-Review-3
content type line 23
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.
Telephone: +65-65165456 Fax: +65-68739664
Correspondence to: Dr. Alan Prem Kumar, PhD, Cancer Science Institute of Singapore, National University of Singapore, Singapore City 117597, Singapore. csiapk@nus.edu.sg
ISSN:1007-9327
2219-2840
2219-2840
DOI:10.3748/wjg.v21.i43.12261