Therapeutic potential of targeting mTOR in T-cell acute lymphoblastic leukemia (Review)

Evangelisti,Camilla; Evangelisti,Cecilia; Chiarini,Francesca; Lonetti,Annalisa; Buontempo,Francesca; Bressanin,Daniela; Cappellini,Alessandra; Orsini,Ester; McCubrey,James  A.; Martelli,Alberto  M.

doi:10.3892/ijo.2014.2525

Therapeutic potential of targeting mTOR in T-cell acute lymphoblastic leukemia (Review)

Authors:
- Camilla Evangelisti
- Cecilia Evangelisti
- Francesca Chiarini
- Annalisa Lonetti
- Francesca Buontempo
- Daniela Bressanin
- Alessandra Cappellini
- Ester Orsini
- James A. McCubrey
- Alberto M. Martelli
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Affiliations: Institute of Molecular Genetics, National Research Council, Rizzoli Orthopedic Institute, Bologna, Italy, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy, Department of Human Social and Health Sciences, University of Cassino, Cassino, Italy, Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA
Published online on: June 26, 2014 https://doi.org/10.3892/ijo.2014.2525
Pages: 909-918

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Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous neoplastic disorder of immature hematopoietic precursors committed to the T-cell lineage. T-ALL comprises about 15% of pediatric and 25% of adult ALL cases. Even if the prognosis of T-ALL has improved especially in the childhood due to the use of new intensified treatment protocols, the outcome of relapsed patients who are resistant to conventional chemotherapeutic drugs or who relapse is still poor. For this reason, there is a need for novel and less toxic targeted therapies against signaling pathways aberrantly activated in T-ALL, such as the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR). Small molecules designed to target key components of this signaling axis have proven their efficacy both in vitro and in vivo in pre-clinical settings of T-ALL. In particular, different classes of mTOR inhibitors have been disclosed by pharmaceutical companies, and they are currently being tested in clinical trials for treating T-ALL patients. One of the most promising approaches for the treatment of T-ALL seems to be the combination of mTOR inhibitors with traditional chemotherapeutic agents. This could lead to a lower drug dosage that may circumvent the systemic side effects of chemotherapeutics. In this review, we focus on the different classes of mTOR inhibitors that will possibly have an impact on the therapeutic arsenal we have at our disposal against T-ALL.

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