| Autor: |
Minilik Angagaw, Kaiko Kunii, Leigh Zawel, Marlene C. Hinton, Chris Winter, Weisheng Zhang, Christopher Ware, Clay L. Efferson, Cloud P. Paweletz, Stephen Fawell, Jennifer Tammam, Brian B. Haines, Pradip K. Majumder, Theresa Zhang, Jonathan D. Cheng, Sriram Sathyanarayanan, Heike Keilhack, Joe Zhu, Gary Gilliland |
| Rok vydání: |
2012 |
| Předmět: |
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| Zdroj: |
Translational Oncology. 5(6):422-429 |
| ISSN: |
1936-5233 |
| DOI: |
10.1593/tlo.12241 |
| Popis: |
Activation of the phosphoinositide 3-kinase pathway is commonly observed in human prostate cancer. Loss of function of phosphatase and tensin homolog (PTEN) is associated with the activation of AKT and mammalian target of rapamycin (mTOR) in many cancer cell lines as well as in other model systems. However, activation of mTOR is also dependent of kinases other than AKT. Here, we show that activation of mTOR is not dependent on AKT in a prostate-specific PTEN-deficient mouse model of prostate cancer. Pathway bifurcation of AKT and mTOR was noted in both mouse and human prostate tumors. We demonstrated for the first time that cotargeting mTOR and AKT with ridaforolimus/MK-8669 and M1K-2206, respectively, delivers additive antitumor effects in vivo when compared to single agents. Our preclinical data suggest that the combination of AKT and mTOR inhibitors might be more effective in treating prostate cancer patients than current treatment regimens or either treatment alone. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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