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Hsp90 inhibitor 17‐AAG inhibits progression of LuCaP35 xenograft prostate tumors to castration resistance
Author(s) -
O'Malley Katherine J.,
Langmann Gabrielle,
Ai Junkui,
RamosGarcia Raquel,
Vessella Robert L.,
Wang Zhou
Publication year - 2011
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22458
Subject(s) - prostate cancer , castration , medicine , prostate , androgen , androgen deprivation therapy , cancer research , cancer , oncology , hormone
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. Prostate 72:1117–1123, 2012. © 2011 Wiley Periodicals, Inc.