The Role of mTOR Signaling as a Therapeutic Target in Cancer

Int J Mol Sci. 2021 Feb 9;22(4):1743. doi: 10.3390/ijms22041743.

Abstract

The aim of this review was to summarize current available information about the role of phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling in cancer as a potential target for new therapy options. The mTOR and PI3K/AKT/mTORC1 (mTOR complex 1) signaling are critical for the regulation of many fundamental cell processes including protein synthesis, cell growth, metabolism, survival, catabolism, and autophagy, and deregulated mTOR signaling is implicated in cancer, metabolic dysregulation, and the aging process. In this review, we summarize the information about the structure and function of the mTOR pathway and discuss the mechanisms of its deregulation in human cancers including genetic alterations of PI3K/AKT/mTOR pathway components. We also present recent data regarding the PI3K/AKT/mTOR inhibitors in clinical studies and the treatment of cancer, as well the attendant problems of resistance and adverse effects.

Keywords: AKT; PI3K; cancer; mTOR; mutation; therapy.

Publication types

  • Review

MeSH terms

  • Autophagy / drug effects
  • Autophagy / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm / genetics
  • Humans
  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Molecular Targeted Therapy / methods
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*
  • Treatment Outcome

Substances

  • Protein Kinase Inhibitors
  • MTOR protein, human
  • Phosphatidylinositol 3-Kinase
  • AKT1 protein, human
  • Mechanistic Target of Rapamycin Complex 1
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases