Abstract 4485: Everolimus reduces androgen dependent and independent prostate cancer in the prostate specific PTEN conditional gene targeting mouse model

• Published in: Cancer research (Chicago, Ill.) Ill.), 2010-04, Vol.70 (8_Supplement), p.4485-4485
• Main Authors: De Velasco, Marco A., Asahi, Chiori, Miyazaki, Yuka, Ushida, Hiroshi, Shimada, Keiji, Yoshikawa, Kazuhiro, Nishio, Kazuto, Konishi, Noboru, Uemura, Hirotsugu
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM10-4485

PTEN deletion is common in castrate resistant prostate cancer (CRPC) with bi-allelic loss correlating to disease-specific mortality and is associated with Akt and AR deregulation. Due to the lack of effective treatment options, new targets for chemotherapy need to be identified. The PI3K/AKT/mTOR pathway is an attractive target and mTOR is one of the most focused targets for small molecule inhibitors. We investigated the treatment efficacy of the mTOR inhibitor, everolimus alone or in combination with the androgen agonist chlormadinone acetate (CA) on non-CRPC and CRPC using our prostate specific PTEN conditional gene targeting mouse model. Sixteen-week-old mice were gavaged with everolimus (10 mg/kg 3x/week) and/or injected subcutaneously with CA (50 mg/kg 3X/week) for 4 weeks. For the CRPC model, mice were castrated at 8 weeks of age and then gavaged with everolimus for 4 weeks starting at 16 weeks of age. The genitourinary tracts (GUTs), were collected, weighed, and imaged. GUT weights were significantly lower in all treatments groups compared to controls in the non-CRPC model (P