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    The phosphatidylinositol 3-kinase/Akt/mTOR signaling network as a therapeutic target in acute myelogenous leukemia patients

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    Author
    Martelli, Alberto M.; Evangelisti, Camilla; Chiarini, Francesca; McCubrey, James A.
    Abstract
    The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling axis plays a central role in cell proliferation, growth, and survival under physiological conditions. However, aberrant PI3K/Akt/mTOR signaling has been implicated in many human cancers, including acute myelogenous leukemia (AML). Therefore, the PI3K/Akt/mTOR network is considered as a validated target for innovative cancer therapy. The limit of acceptable toxicity for standard polychemotherapy has been reached in AML. Novel therapeutic strategies are therefore needed. This review highlights how the PI3K/Akt/mTOR signaling axis is constitutively active in AML patients, where it affects survival, proliferation, and drug-resistance of leukemic cells including leukemic stem cells. Effective targeting of this pathway with small molecule kinase inhibitors, employed alone or in combination with other drugs, could result in the suppression of leukemic cell growth. Furthermore, targeting the PI3K/Akt/mTOR signaling network with small pharmacological inhibitors, employed either alone or in combinations with other drugs, may result in less toxic and more efficacious treatment of AML patients. Efforts to exploit pharmacological inhibitors of the PI3K/Akt/mTOR cascade which show efficacy and safety in the clinical setting are now underway.
    URI
    http://hdl.handle.net/10342/5656
    Subject
     PI3K/Akt/mTOR; leukemia; leukemic stem cells; signal transduction modulators; targeted therapy; combination therapy 
    Date
    2010-06
    Citation:
    APA:
    Martelli, Alberto M., & Evangelisti, Camilla, & Chiarini, Francesca, & McCubrey, James A.. (June 2010). The phosphatidylinositol 3-kinase/Akt/mTOR signaling network as a therapeutic target in acute myelogenous leukemia patients. Oncotarget, (1:2), p.89-103. Retrieved from http://hdl.handle.net/10342/5656

    Display/Hide MLA, Chicago and APA citation formats.

    MLA:
    Martelli, Alberto M., and Evangelisti, Camilla, and Chiarini, Francesca, and McCubrey, James A.. "The phosphatidylinositol 3-kinase/Akt/mTOR signaling network as a therapeutic target in acute myelogenous leukemia patients". Oncotarget. 1:2. (89-103.), June 2010. August 10, 2022. http://hdl.handle.net/10342/5656.
    Chicago:
    Martelli, Alberto M. and Evangelisti, Camilla and Chiarini, Francesca and McCubrey, James A., "The phosphatidylinositol 3-kinase/Akt/mTOR signaling network as a therapeutic target in acute myelogenous leukemia patients," Oncotarget 1, no. 2 (June 2010), http://hdl.handle.net/10342/5656 (accessed August 10, 2022).
    AMA:
    Martelli, Alberto M., Evangelisti, Camilla, Chiarini, Francesca, McCubrey, James A.. The phosphatidylinositol 3-kinase/Akt/mTOR signaling network as a therapeutic target in acute myelogenous leukemia patients. Oncotarget. June 2010; 1(2) 89-103. http://hdl.handle.net/10342/5656. Accessed August 10, 2022.
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