PURPOSE OF REVIEW: 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).
RECENT FINDINGS: 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.
SUMMARY: 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.
Written by:
Ischia J, Saad F, Gleave M. Are you the author?
Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia; The Division of Urology, University of Montreal Hospital Center (CHUM), University of Montreal, Montreal, Quebec, Canada.
Reference: Curr Opin Urol. 2013 Feb 4. Epub ahead of print.
doi: 10.1097/MOU.0b013e32835e9f1a
PubMed Abstract
PMID: 23385973
