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    Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update

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    Author
    Evangelisti, Camilla; Chiarini, Francesca; McCubrey, James A.; Martelli, Alberto M.
    Abstract
    T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive blood malignancy that arises from the clonal expansion of transformed T-cell precursors. Although T-ALL prognosis has significantly improved due to the development of intensive chemotherapeutic protocols, primary drug-resistant and relapsed patients still display a dismal outcome. In addition, lifelong irreversible late effects from conventional therapy are a growing problem for leukemia survivors. Therefore, novel targeted therapies are required to improve the prognosis of high-risk patients. The mechanistic target of rapamycin (mTOR) is the kinase subunit of two structurally and functionally distinct multiprotein complexes, which are referred to as mTOR complex 1 (mTORC1) and mTORC2. These two complexes regulate a variety of physiological cellular processes including protein, lipid, and nucleotide synthesis, as well as autophagy in response to external cues. However, mTOR activity is frequently deregulated in cancer, where it plays a key oncogenetic role driving tumor cell proliferation, survival, metabolic transformation, and metastatic potential. Promising preclinical studies using mTOR inhibitors have demonstrated efficacy in many human cancer types, including T-ALL. Here, we highlight our current knowledge of mTOR signaling and inhibitors in T-ALL, with an emphasis on emerging evidence of the superior efficacy of combinations consisting of mTOR inhibitors and either traditional or targeted therapeutics.
    URI
    http://hdl.handle.net/10342/8003
    Date
    2018-06-26
    Citation:
    APA:
    Evangelisti, Camilla, & Chiarini, Francesca, & McCubrey, James A., & Martelli, Alberto M.. (June 2018). Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update. International Journal of Molecular Sciences, (19:7), p.. Retrieved from http://hdl.handle.net/10342/8003

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    MLA:
    Evangelisti, Camilla, and Chiarini, Francesca, and McCubrey, James A., and Martelli, Alberto M.. "Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update". International Journal of Molecular Sciences. 19:7. (.), June 2018. March 03, 2021. http://hdl.handle.net/10342/8003.
    Chicago:
    Evangelisti, Camilla and Chiarini, Francesca and McCubrey, James A. and Martelli, Alberto M., "Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update," International Journal of Molecular Sciences 19, no. 7 (June 2018), http://hdl.handle.net/10342/8003 (accessed March 03, 2021).
    AMA:
    Evangelisti, Camilla, Chiarini, Francesca, McCubrey, James A., Martelli, Alberto M.. Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update. International Journal of Molecular Sciences. June 2018; 19(7) . http://hdl.handle.net/10342/8003. Accessed March 03, 2021.
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