PI3K/Akt/mTOR inhibitors in cancer: At the bench and bedside

Semin Cancer Biol. 2019 Dec:59:125-132. doi: 10.1016/j.semcancer.2019.07.009. Epub 2019 Jul 16.

Abstract

Phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway is one of the major cellular signaling pathways that plays an important role in basic intracellular functions. The PI3K/Akt/mTOR pathway regulates cell proliferation, growth, cell size, metabolism, and motility. Component genes of this pathway have been extensively studied and found to be commonly activated in human cancer. Inhibition of this pathway has been shown to lead to regression of human tumors and has been studied in preclinical setup and evaluated in many clinical trials at various levels. Some inhibitors of this pathway are approved by the Food and Drug Administration after their potency and safety have been shown in clinical trials. This review discusses the recent trends in exploiting the PI3K/Akt/mTOR pathway towards the molecular targeted therapy using small molecule inhibitors in human cancer.

Keywords: Akt; Cancer; Inhibitors; PI3K; mTOR.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Humans
  • Molecular Targeted Therapy* / methods
  • Neoplasms / drug therapy*
  • Neoplasms / etiology
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors / pharmacology
  • Phosphoinositide-3 Kinase Inhibitors / therapeutic use*
  • Prognosis
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • Treatment Outcome

Substances

  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases