title: Hsp90 inhibitor 17-AAG inhibits progression of LuCaP35 xenograft prostate tumors to castration resistance.
abstract: BACKGROUND
  Advanced prostate cancer is currently treated with androgen deprivation therapy (ADT). ADT initially results in tumor regression; however, all patients eventually relapse with castration-resistant prostate cancer. New approaches to delay the progression of prostate cancer to castration resistance are in desperate need. This study addresses whether targeting Heat shock protein 90 (HSP90) regulation of androgen receptor (AR) can inhibit prostate cancer progression to castration resistance.
  
  
  METHODS
  The HSP90 inhibitor 17-AAG was injected intraperitoneally into nude mice bearing LuCaP35 xenograft tumors to determine the effect of HSP90 inhibition on prostate cancer progression to castration resistance and host survival.
  
  
  RESULTS
  Administration of 17-AAG maintained androgen-sensitivity, delayed the progression of LuCaP35 xenograft tumors to castration resistance, and prolonged the survival of host. In addition, 17-AAG prevented nuclear localization of endogenous AR in LuCaP35 xenograft tumors in castrated nude mice.
  
  
  CONCLUSIONS
  Targeting Hsp90 or the mechanism by which HSP90 regulates androgen-independent AR nuclear localization and activation may lead to new approaches to prevent and/or treat castration-resistant prostate cancer.
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: O'Malley
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Langmann
authors.forename: Junkui
authors.initials: J
authors.lastname: Ai
authors.forename: Raquel
authors.initials: R
authors.lastname: Ramos-Garcia
authors.forename: Robert L
authors.initials: RL
authors.lastname: Vessella
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D018450:Disease Progression; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047029:Lactams, Macrocyclic / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
chemical_list: D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; C112765:tanespimycin