Recent studies of 5-fluorouracil resistance in pancreatic cancer.
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.
Wei-Bin Wang, Yu Yang, Yu-Pei Zhao, Tai-Ping Zhang, Quan Liao, Hong Shu, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
Wei-Bin
WB
Wang
Wei-Bin Wang, Yu Yang, Yu-Pei Zhao, Tai-Ping Zhang, Quan Liao, Hong Shu, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
Yu
Y
Yang
Wei-Bin Wang, Yu Yang, Yu-Pei Zhao, Tai-Ping Zhang, Quan Liao, Hong Shu, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
Yu-Pei
YP
Zhao
Wei-Bin Wang, Yu Yang, Yu-Pei Zhao, Tai-Ping Zhang, Quan Liao, Hong Shu, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
Tai-Ping
TP
Zhang
Wei-Bin Wang, Yu Yang, Yu-Pei Zhao, Tai-Ping Zhang, Quan Liao, Hong Shu, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
Quan
Q
Liao
Wei-Bin Wang, Yu Yang, Yu-Pei Zhao, Tai-Ping Zhang, Quan Liao, Hong Shu, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
Hong
H
Shu
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005472:Fluorouracil / Q000378:metabolism / Q000627:therapeutic use*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D040901:Proteomics / Q000379:methods
D000964:Antimetabolites, Antineoplastic; D026901:Membrane Transport Proteins; D035683:MicroRNAs; D005472:Fluorouracil
5-fluorouracil; Metabolic enzyme; MicroRNA; Proteomic investigation; Resistance; Signaling pathway; Stromal factors; Transporters