title: Targeting the PI3K/Akt signaling pathway in gastric carcinoma: A reality for personalized medicine?
abstract: 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.
authors.affiliation: 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.
authors.forename: Shikha Satendra
authors.initials: SS
authors.lastname: Singh
authors.affiliation: 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.
authors.forename: Wei Ney
authors.initials: WN
authors.lastname: Yap
authors.affiliation: 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.
authors.forename: Frank
authors.initials: F
authors.lastname: Arfuso
authors.affiliation: 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.
authors.forename: Shreya
authors.initials: S
authors.lastname: Kar
authors.affiliation: 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.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Wanpei
authors.initials: W
authors.lastname: Cai
authors.affiliation: 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.
authors.forename: Arunasalam M
authors.initials: AM
authors.lastname: Dharmarajan
authors.affiliation: 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.
authors.forename: Gautam
authors.initials: G
authors.lastname: Sethi
authors.affiliation: 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.
authors.forename: Alan Prem
authors.initials: AP
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D058990:Molecular Targeted Therapy; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: Epidemiology; Gastric cancer; PI3K/Akt/mTOR pathway; Predictive biomarkers; Targeted therapy