title: Inhibition of tumor growth progression by antiandrogens and mTOR inhibitor in a Pten-deficient mouse model of prostate cancer.
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.
authors.affiliation: Department of Imaging, Merck Research Laboratories, Boston, Massachusetts 02115, USA. weisheng_zhang@merck.com
authors.forename: Weisheng
authors.initials: W
authors.lastname: Zhang
authors.forename: Joe
authors.initials: J
authors.lastname: Zhu
authors.forename: Clay L
authors.initials: CL
authors.lastname: Efferson
authors.forename: Chris
authors.initials: C
authors.lastname: Ware
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tammam
authors.forename: Minilik
authors.initials: M
authors.lastname: Angagaw
authors.forename: Jason
authors.initials: J
authors.lastname: Laskey
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Bettano
authors.forename: Shailaja
authors.initials: S
authors.lastname: Kasibhatla
authors.forename: John F
authors.initials: JF
authors.lastname: Reilly
authors.forename: Cyrille
authors.initials: C
authors.lastname: Sur
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Majumder
mesh_terms: D000726:Androgen Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism*; D048708:Cell Growth Processes / Q000187:drug effects; D021621:Imaging, Three-Dimensional / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D051058:Oncogene Protein v-akt / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D020123:Sirolimus / Q000008:administration & dosage / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases; D014463:Ultrasonography / Q000379:methods
chemical_list: D000726:Androgen Antagonists; D002352:Carrier Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C546843:mTOR protein, mouse; D051058:Oncogene Protein v-akt; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D020123:Sirolimus