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Inhibition of Tumor Growth Progression by Antiandrogens and mTOR Inhibitor in a Pten-Deficient Mouse Model of Prostate Cancer

Departments of ¹ Imaging, ² Oncology, ³ Pharmacology, and ⁴ Laboratory Animal Research, Merck Research Laboratories, Boston, Massachusetts; and ⁵ Imaging Department, Merck Research Laboratories, West Point, Pennsylvania

Requests for reprints: Weisheng Zhang, Imaging Department, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115. Phone: 617-992-3061; Fax: 617-992-2487; E-mail: weisheng_zhang{at}merck.com and Pradip K. Majumder, Department of Oncology, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115. Phone: 617-992-2281; Fax: 617-992-2486; E-mail: pradip_majumder{at}merck.com.

Key Words: PTEN • prostate tumor • ultrasound imaging • androgen receptor • Casodex • mTOR

Androgen receptors have been shown to play a critical role in prostate cancer. We used ultrasound imaging techniques to track tumor response to antiandrogen and rapamycin treatment in a prostate-specific Pten-deleted mouse model of cancer. Depletion of androgens by either surgical or chemical castration significantly inhibited tumor growth progression without altering the activation of Akt and mammalian target of rapamycin (mTOR). We also showed for the first time that targeting mTOR along with antiandrogen treatment exhibited additive antitumor effects in vivo when compared with single agents. Our preclinical data suggest that combination of antiandrogens with mTOR inhibitors might be more effective in treating androgen-dependent prostate cancer patients. [Cancer Res 2009;69(18):7466–72]