title: Genexol inhibits primary tumour growth and metastases in gemcitabine-resistant pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  Gemcitabine, the current standard of care for pancreatic ductal adenocarcinoma (PDA), has a less than 10% partial response rate. Genexol-PM, a modified form of paclitaxel, has been shown to have antitumour effects in clinical trials of metastatic breast and small-lung-cell carcinoma. The aim of the present study was to determine if Genexol would be a beneficial treatment for gemcitabine-resistant PDA.
  
  
  METHODS
  We measured the in vitro IC50s of gemcitabine and genexol in cell lines sensitive and resistant to gemcitabine. In vivo, animals with orthotopic pancreatic tumours, resistant to gemcitabine, were treated with phosphate-buffered saline (PBS), gemcitabine, Genexol or gemcitabine+Genexol. Tumour progression was monitored using red fluorescent protein imaging.
  
  
  RESULTS
  We showed equivalent IC50s for gemcitabine-sensitive and gemcitabine-resistant cell lines when treated with genexol. In vivo treatment with genexol resulted in a greater per cent reduction in tumour size, less metastatic spread and longer survival compared with treatment with gemcitabine.
  
  
  CONCLUSIONS
  Genexol proved to be an effective treatment for gemcitabine-resistant PDA. These data combined with the successful clinical use of genexol in Phase II trials of other malignancies suggests it maybe an effective treatment for pancreatic cancer, specifically for those patients resistant to gemcitabine.
authors.affiliation: Department of Surgery, School of Medicine, University of Utah, Salt Lake City, UT 84132, USA.
authors.forename: Jill E
authors.initials: JE
authors.lastname: Shea
authors.forename: Kweon-Ho
authors.initials: KH
authors.lastname: Nam
authors.forename: Natalya
authors.initials: N
authors.lastname: Rapoport
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Scaife
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000556:secondary; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine