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Targeting PI3K/AKT/mTOR network for treatment of leukemia

Jessika Bertacchini1, Nazanin Heidari, Laura Mediani

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

Cellular and Molecular Life Sciences : CMLS
|February 26, 2015
PubMed
Abstract

Insights

Targeting the phosphoinositide 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway shows therapeutic promise in various leukemias. Inhibitors targeting this pathway demonstrate superior efficacy compared to conventional treatments in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The phosphoinositide 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is frequently hyperactivated in malignancies.
  • This pathway plays a critical role in the survival of leukemia stem cells and early leukemic precursors.
  • Inhibition of the PI3K/AKT/mTOR pathway is a recognized therapeutic strategy for leukemia.

Purpose of the Study:

  • To review and evaluate the efficacy of PI3K/AKT/mTOR inhibitors in preclinical leukemia models.
  • To assess the therapeutic potential of targeting the PI3K/AKT/mTOR pathway in various types of leukemia.

Main Methods:

  • Review of existing literature on PI3K/AKT/mTOR inhibitors in leukemia.
  • Analysis of in vitro studies using leukemia cell lines.
  • Analysis of in vivo studies using animal models of leukemia.

Main Results:

  • Inhibition of the PI3K/AKT/mTOR pathway exhibits beneficial therapeutic effects in both in vitro and in vivo leukemia models.
  • Various inhibitors, including dual PI3K/mTOR, dual Akt/RTK, Akt, selective PI3K, mTOR, and dual PI3K/PDK1 inhibitors, show improved outcomes in CML, AML, APL, CLL, B-ALL, and T-ALL compared to conventional treatments.
  • Targeting this pathway demonstrates pro-apoptotic and antiproliferative effects on hematological malignancies.

Conclusions:

  • PI3K/AKT/mTOR pathway inhibition offers a promising therapeutic avenue for leukemias.
  • Specific classes of inhibitors show superior efficacy in diverse leukemia subtypes.
  • Modulation of microRNA (miRNA) presents a novel approach for regulating this pathway, warranting further clinical investigation.

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