Published online Nov 14, 2014. doi: 10.3748/wjg.v20.i42.15682
Revised: May 4, 2014
Accepted: July 24, 2014
Published online: November 14, 2014
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.
Core tip: 5-fluorouracil (5-FU) is one of the most important drugs for human pancreatic cancer. Although recent studies have questioned the effectiveness of 5-FU against pancreatic cancer, it remains a good choice for pancreatic cancer. Our paper discusses recent studies that provide novel insights into 5-FU chemotherapy in pancreatic cancer.