Inhibition of tumor growth progression by antiandrogens and mTOR inhibitor in a Pten-deficient mouse model of prostate cancer

抗雄激素和 mTOR 抑制剂在 Pten 缺陷小鼠前列腺癌模型中抑制肿瘤生长进展

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作者:Weisheng Zhang, Joe Zhu, Clay L Efferson, Chris Ware, Jennifer Tammam, Minilik Angagaw, Jason Laskey, Kimberly A Bettano, Shailaja Kasibhatla, John F Reilly, Cyrille Sur, Pradip K Majumder

Abstract

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.

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