Biological Aspects of mTOR in Leukemia

Int J Mol Sci. 2018 Aug 14;19(8):2396. doi: 10.3390/ijms19082396.

Abstract

The mammalian target of rapamycin (mTOR) is a central processor of intra- and extracellular signals, regulating many fundamental cellular processes such as metabolism, growth, proliferation, and survival. Strong evidences have indicated that mTOR dysregulation is deeply implicated in leukemogenesis. This has led to growing interest in the development of modulators of its activity for leukemia treatment. This review intends to provide an outline of the principal biological and molecular functions of mTOR. We summarize the current understanding of how mTOR interacts with microRNAs, with components of cell metabolism, and with controllers of apoptotic machinery. Lastly, from a clinical/translational perspective, we recapitulate the therapeutic results in leukemia, obtained by using mTOR inhibitors as single agents and in combination with other compounds.

Keywords: apoptosis; cell signaling; leukemia; mTOR inhibitors; metabolism; miRNA.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Humans
  • Leukemia / drug therapy
  • Leukemia / enzymology*
  • MicroRNAs / metabolism
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / metabolism*
  • Protein Kinase Inhibitors / therapeutic use
  • RNA, Neoplasm / metabolism
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • MicroRNAs
  • Neoplasm Proteins
  • Protein Kinase Inhibitors
  • RNA, Neoplasm
  • MTOR protein, human
  • TOR Serine-Threonine Kinases