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Targeting PI3K/AKT/mTOR network for treatment of leukemia

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Abstract

Objective

Increased activity of PI3K/AKT/mTOR pathway has been observed in a huge number of malignancies. This pathway can function as a prosurvival factor in leukemia stem cells and early committed leukemic precursors and its inhibition is regarded as a therapeutic approach. Accordingly, the aim of this review is to evaluate the PI3K/Akt/mTOR inhibitors used in leukemia models.

Discussion

Inhibition of the PI3K/AKT/mTOR pathway has been reported to have beneficial therapeutic effects in leukemias, both in vitro in leukemia cell lines and in vivo in animal models. Overall, the use of dual PI3K/mTOR inhibitor, dual Akt/RTK inhibitor, Akt inhibitor, selective inhibitor of PI3K, mTOR inhibitor and dual PI3K/PDK1 inhibitor in CML, AML, APL, CLL, B-ALL and T-ALL has a better therapeutic effect than conventional treatments.

Conclusions

Targeting the PI3K/Akt/mTOR pathway may have pro-apoptotic and antiproliferative effects on hematological malignancies. Furthermore, modulation of miRNA can be used as a novel therapeutic approach to regulate the PI3K/Akt/mTOR pathway. However, both aspects require further clinical studies.

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Authors and Affiliations

  1. Department of Surgery, Medicine, Dentistry and Morphology, University of Modena and Reggio Emilia, Modena, Italy

    Jessika Bertacchini & Laura Mediani

  2. Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy

    Jessika Bertacchini & Silvano Capitani

  3. Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Nazanin Heidari, Mohammad Shahjahani, Ahmad Ahmadzadeh & Najmaldin Saki

  4. LTTA Center, University of Ferrara, Ferrara, Italy

    Silvano Capitani

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  1. Jessika Bertacchini
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  2. Nazanin Heidari
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Bertacchini, J., Heidari, N., Mediani, L. et al. Targeting PI3K/AKT/mTOR network for treatment of leukemia. Cell. Mol. Life Sci. 72, 2337–2347 (2015). https://doi.org/10.1007/s00018-015-1867-5

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  • DOI: https://doi.org/10.1007/s00018-015-1867-5

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