Regulation and importance of the PI3K/Akt/mTOR signaling pathway in hematologic malignancies

Anticancer Agents Med Chem. 2009 Nov;9(9):1024-38. doi: 10.2174/187152009789377772.

Abstract

Phosphatidylinositol 3-kinase (PI3K), a heterodimeric lipid kinase, is a key enzyme in signal transduction from various stimuli to downstream pathways that elicit diverse responses involving growth, proliferation, survival, differentiation, and metabolism in many cellular systems. Activated PI3K generates phosphatidylinositol-3,4,5-triphosphate, which recruits phosphatidylinositol-dependent kinase 1 (PDK1) and Akt serine/threonine kinase at the plasma membrane, resulting in activation of Akt. In turn, Akt activates multiple downstream targets, most notably the mTOR pathway. There is abundant evidence implicating the PI3K/Akt/mTOR pathway in the development and progression of a variety of tumors including hematologic neoplasms. Therefore, this pathway is considered a critical target for cancer therapy. We review the regulatory mechanisms of the PI3K/Akt/mTOR signaling pathway and the role of this pathway in oncogenesis of hematological malignancies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Hematologic Neoplasms / enzymology
  • Hematologic Neoplasms / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protein Isoforms / metabolism
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • TOR Serine-Threonine Kinases

Substances

  • Intracellular Signaling Peptides and Proteins
  • Protein Isoforms
  • Phosphatidylinositol 3-Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt