title: Targeting HSP90 by the novel inhibitor NVP-AUY922 reduces growth and angiogenesis of pancreatic cancer.
abstract: OBJECTIVE
  To evaluate the impact of heat-shock protein 90 (HSP90) blockade by the novel inhibitor NVP-AUY922, on tumor growth and angiogenesis in pancreatic cancer.
  
  
  METHODS
  Effects of NVP-AUY922 on signaling pathways were evaluated by western blotting. Cell motility of cancer cells, pericytes and endothelial cells was investigated in Boyden chambers. Impact of HSP90 blockade on pancreatic tumor growth and angiogenesis were studied in in vivo tumor models.
  
  
  RESULTS
  NVP-AUY922 effectively inhibited cancer cell growth. Moreover, HSP90 inhibition potently interfered with multiple signaling pathways in cancer cells, as well as endothelial cells and pericytes, leading to significant reduction of pro-migratory and invasive properties of these cell types. In vivo, treatment with NVP-AUY922 significantly inhibited growth and vascularization of pancreatic cancer at doses far below the maximum tolerated dose.
  
  
  CONCLUSIONS
  HSP90 blockade by the novel synthetic inhibitor NVP-AUY922 effectively reduces pancreatic cancer progression through direct effects on cancer cells, as well as on endothelial cells and pericytes.
authors: Department of Surgery, University of Regensburg Medical Center, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. christian.moser@ukr.de
authors: Christian
authors: C
authors: Moser
authors: Sven A
authors: SA
authors: Lang
authors: Christina
authors: C
authors: Hackl
authors: Christine
authors: C
authors: Wagner
authors: Eva
authors: E
authors: Scheiffert
authors: Hans J
authors: HJ
authors: Schlitt
authors: Edward K
authors: EK
authors: Geissler
authors: Oliver
authors: O
authors: Stoeltzing
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D011897:Random Allocation; D012118:Resorcinols / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: C528044:5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide; D018841:HSP90 Heat-Shock Proteins; D007555:Isoxazoles; D012118:Resorcinols