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Glucose metabolic phenotype of pancreatic cancer

Glucose metabolic phenotype of pancreatic cancer

作     者:Anthony KC Chan Jason IE Bruce Ajith K Siriwardena 

作者机构:Regional Hepato-Pancreato-Biliary Surgery Unit Manchester Royal Infirmary Faculty of Life Sciences University of Manchester 

出 版 物:《World Journal of Gastroenterology》 (世界胃肠病学杂志(英文版))

年 卷 期:2016年第22卷第12期

页      面:3471-3485页

核心收录:

学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主  题:Metabolism Pancreatic cancer Warburg effect Metabolic inhibitor Glycolysis Krebs cycle 

摘      要:AIM: To construct a global metabolic phenotype of pancreatic ductal adenocarcinoma(PDAC) reflecting tumour-related metabolic enzyme ***: A systematic review of the literature was performed using Ovid SP and Pub Med databases using keywords pancreatic cancer and individual glycolytic and mitochondrial oxidative phosphorylation(MOP) enzymes. Both human and animal studies investigating the oncological effect of enzyme expression changes and inhibitors in both an in vitro and in vivo setting were included in the review. Data reporting changes in enzyme expression and the effects on PDAC cells, such as survival and metastatic potential, were extracted to construct a metabolic phenotype. RESULTS: Seven hundred and ten papers were initially retrieved, and were screened to meet the review inclusion criteria. 107 unique articles were identified as reporting data involving glycolytic enzymes, and 28 articles involving MOP enzymes in PDAC. Data extraction followed a pre-defined protocol. There is consistent over-expression of glycolytic enzymes and lactate dehydrogenase in keeping with the Warburg effect to facilitate rapid adenosine-triphosphate production from glycolysis. Certain isoforms of these enzymes were over-expressed specifically in PDAC. Altering expression levels of HK, PGI, FBA, enolase, PK-M2 and LDA-A with metabolic inhibitors have shown a favourable effect on PDAC, thus identifying these as potential therapeutic targets. However, the Warburg effect on MOP enzymes is less clear, with different expression levels at different points in the Krebs cycle resulting in a fundamental change of metabolite levels, suggesting that other essential anabolic pathways are being stimulated. CONCLUSION: Further characterisation of the PDAC metabolic phenotype is necessary as currently there are few clinical studies and no successful clinical trials targeting metabolic enzymes.

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