title: The promise of heat shock protein inhibitors in the treatment of castration resistant prostate cancer.
abstract: OBJECTIVE
  To present the recent advances in novel agents that target heat shock proteins (Hsps) to treat or delay the development of castration resistant prostate cancer (CRPC).
  
  
  RESULTS
  Multiple preclinical studies have shown that silencing Hsp27, Hsp90, or clusterin sensitizes prostate cancer cells to modern chemotherapy and radiation treatments; and overexpression of these chaperones confers resistance to these therapies. Antisense oligonucleotides targeting Hsp27 and clusterin have shown good biological activity in human phase II trials and phase III studies are ongoing. Despite promising preclinical efficacy, a number of phase I/II human trials with various Hsp90 inhibitors have been disappointing with negligible anticancer activity and dose-limiting toxicity profiles. Newer Hsp90 inhibitors with better toxicity profiles, and inhibitors that target Hsp90 cofactors, such as FKBP52, are currently being investigated in human studies.
  
  
  CONCLUSIONS
  Many Hsp chaperone client proteins are key components of alternative growth factor pathways upregulated in CRPC and are involved in key resistance pathways to current chemotherapy and radiotherapy regimes. New treatments that inhibit Hsps are attractive anticancer strategies as they have the ability to simultaneously target multiple pathways involved in CRPC.
authors: Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia bThe Division of Urology, University of Montreal Hospital Center (CHUM), University of Montreal, Montreal, Quebec, Canada.
authors: Joseph
authors: J
authors: Ischia
authors: Fred
authors: F
authors: Saad
authors: Martin
authors: M
authors: Gleave
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008297:Male; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins