Hsp90 inhibitor 17‐AAG inhibits progression of LuCaP35 xenograft prostate tumors to castration resistance

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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. Prostate 72:1117–1123, 2012.

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