期刊
WORLD JOURNAL OF GASTROENTEROLOGY
卷 20, 期 42, 页码 15682-15690出版社
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.3748/wjg.v20.i42.15682
关键词
5-fluorouracil; Resistance; Transporters; Metabolic enzyme; Signaling pathway; Stromal factors; MicroRNA; Proteomic investigation
资金
- Research Special Fund for the Public Welfare Industry of Health (The Translational Research of Early Diagnosis and Comprehensive Treatment in Pancreatic Cancer) [201202007]
Resistance to 5-fluorouracil (5-FU), an important anticancer drug, is a serious challenge in the treatment of pancreatic cancer. Equilibrative nucleoside transporter 1 and multidrug-resistance protein (MRP) 5 and MRP8, rather than P-glycoprotein, play important roles in 5-FU transport. Thymidylate synthase, dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase and thymidine phosphorylase are four key enzymes involved in 5-FU metabolism. Other metabolic enzymes, including uridine monophosphate synthetase, also contribute to chemoresistance. Intracellular signaling pathways are an integrated network, and nuclear factor kappa-light-chain-enhancer of activated B cells, AKT and extracellular signal-regulated kinases are signaling pathways that are particularly relevant to 5-FU resistance. In addition, recent reports indicate that STAT-3 is a crucial survival protein. Proteomic assays provide a powerful tool for identifying target proteins and understanding the role of microRNAs and stromal factors to facilitate the development of strategies to combat 5-FU resistance. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.
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