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 los...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.展开更多
Tumours are known to be a heterogeneous group of cells,which is why they are difficult to eradicate.One possible cause for this is the existence of slow-cycling cancer stem cells(CSCs)endowed with stem cell-like prope...Tumours are known to be a heterogeneous group of cells,which is why they are difficult to eradicate.One possible cause for this is the existence of slow-cycling cancer stem cells(CSCs)endowed with stem cell-like properties of self-renewal,which are responsible for resistance to chemotherapy and radiotherapy.In recent years,the role of lipid metabolism has garnered increasing attention in cancer.Specifically,the key roles of enzymes such as stearoyl-CoA desaturase-1 and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase in CSCs,have gained particular interest.However,despite accumulating evidence on the role of proteins in controlling lipid metabolism,very little is known about the specific role played by lipid products in CSCs.This review highlights recent findings on the role of lipid metabolism in CSCs,focusing on the specific mechanism by which bioactive lipids regulate the fate of CSCs and their involvement in signal transduction pathways.展开更多
基金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)+1 种基金the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiative to Cancer Science Institute of SingaporeNational University of Singapore and by the NCIS Yong Siew Yoon Research Grant through donations from the Yong Loo Lin Trust(to Kumar AP)
文摘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.
文摘Tumours are known to be a heterogeneous group of cells,which is why they are difficult to eradicate.One possible cause for this is the existence of slow-cycling cancer stem cells(CSCs)endowed with stem cell-like properties of self-renewal,which are responsible for resistance to chemotherapy and radiotherapy.In recent years,the role of lipid metabolism has garnered increasing attention in cancer.Specifically,the key roles of enzymes such as stearoyl-CoA desaturase-1 and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase in CSCs,have gained particular interest.However,despite accumulating evidence on the role of proteins in controlling lipid metabolism,very little is known about the specific role played by lipid products in CSCs.This review highlights recent findings on the role of lipid metabolism in CSCs,focusing on the specific mechanism by which bioactive lipids regulate the fate of CSCs and their involvement in signal transduction pathways.
