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

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 castra...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2009-09, Vol.69 (18), p.7466-7472
Main Authors: WEISHENG ZHANG, ZHU, Joe, SUR, Cyrille, MAJUMDER, Pradip K, EFFERSON, Clay L, WARE, Chris, TAMMAM, Jennifer, ANGAGAW, Minilik, LASKEY, Jason, BETTANO, Kimberly A, KASIBHATLA, Shailaja, REILLY, John F
Format: Article
Language:English
Subjects:
Androgen Antagonists - administration & dosage
Androgen Antagonists - pharmacology
Animals
Antineoplastic agents
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Biological and medical sciences
Carrier Proteins - metabolism
Cell Growth Processes - drug effects
Gynecology. Andrology. Obstetrics
Imaging, Three-Dimensional - methods
Male
Male genital diseases
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Nephrology. Urinary tract diseases
Oncogene Protein v-akt - metabolism
Pharmacology. Drug treatments
Phosphotransferases (Alcohol Group Acceptor) - metabolism
Prostatic Neoplasms - diagnostic imaging
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - pathology
PTEN Phosphohydrolase - deficiency
PTEN Phosphohydrolase - genetics
Sirolimus - administration & dosage
Sirolimus - pharmacology
TOR Serine-Threonine Kinases
Tumors
Tumors of the urinary system
Ultrasonography - methods
Urinary tract. Prostate gland
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-08-4385