PT  - JOURNAL ARTICLE
AU  - Zorn, Christoph S.
AU  - Wojno, Kirk J.
AU  - McCabe, Michael T.
AU  - Kuefer, Rainer
AU  - Gschwend, Juergen E.
AU  - Day, Mark L.
TI  - 5-Aza-2′-Deoxycytidine Delays Androgen-Independent Disease and Improves Survival in the Transgenic Adenocarcinoma of the Mouse Prostate Mouse Model of Prostate Cancer
AID  - 10.1158/1078-0432.CCR-06-2381
DP  - 2007 Apr 01
TA  - Clinical Cancer Research
PG  - 2136--2143
VI  - 13
IP  - 7
4099  - http://clincancerres.aacrjournals.org/content/13/7/2136.short
4100  - http://clincancerres.aacrjournals.org/content/13/7/2136.full
SO  - Clin Cancer Res2007 Apr 01; 13
AB  - Purpose: We have previously shown that 5-aza-2′-deoxycytidine (5-aza) is an effective chemopreventive agent capable of preventing early disease progression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. The purpose of this study was to determine the effect of 5-aza on preexisting TRAMP prostate cancers and prevention of androgen-independent prostate cancer. Experimental Design: TRAMP mice with established prostate cancers were treated with 5-aza, castration, castration + 5-aza, or vehicle control (PBS). One cohort of 22 mice per treatment was euthanized after 10 weeks of treatment, whereas a second cohort of 14 mice per group was followed until death to determine survival. Histologic sections of prostate, pelvic lymph nodes, lung, and liver were blinded and analyzed by a certified genitourinary pathologist (K.J.W.). Results: Combined treatment (castration + 5-aza) provided significant survival benefits over either single treatment (combined versus castration P = 0.029, combined versus 5-aza P = 0.036). At 24 weeks of age, 86% of mice within the PBS cohort exhibited histologic evidence of prostate cancer, whereas only 47% of the combined cohort exhibited malignant disease (P < 0.0001). Additionally, whereas 43% of the PBS treatment group exhibited lymph node metastases, these were only observed in 21% of the combined treatment mice. Conclusions: This is the first study to examine the effect of 5-aza and combined castration + 5-aza on preexisting prostate cancer in an animal model. Based on these preclinical findings, we suggest that 5-aza treatment may prolong the time to an androgen-independent status and thus survival in a hormone-deprived setting in prostate cancer.