Targeting mTOR for the treatment of AML. New agents and new directions

Jessica K. Altman, Antonella Sassano, Leonidas C. Platanias*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Despite recent advances in the field, the treatment of patients with acute myeloid leukemia (AML) remains challenging and difficult. Although chemotherapeutic agents induce remissions in a large number of patients, many of them eventually relapse and die. A major goal for the development of new approaches for the treatment of AML is to enhance the antileukemic effects of standard chemotherapeutics and to design effective combinations targeting non-overlapping cellular pathways. The PI3K/Akt/mTOR signaling pathway plays a critical role in survival and growth of malignant cells and its targeting has been the focus of extensive work and research efforts over the last two decades. It now appears possible that a major limitation of the first generation of mTOR inhibitors can be overcome by a new class of catalytic inhibitors of mTOR. There is emerging evidence that such compounds target both TORC1 and TORC2 and elicit much more potent responses against early leukemic precursors in vitro. In addition, recent studies have shown that combinations of such agents with cytarabine result in enhanced antileukemic responses in vitro, raising the prospect and potential of use of these agents in combination regimens for the treatment of AML.

Original languageEnglish (US)
Pages (from-to)510-517
Number of pages8
JournalOncotarget
Volume2
Issue number6
DOIs
StatePublished - Jun 2011

Keywords

  • Acute myeloid leukemia
  • Cell survival
  • Chemotherapy
  • Kinase
  • Rapamycin
  • Signaling
  • TORC1
  • TORC2
  • mTOR

ASJC Scopus subject areas

  • Oncology

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