PI3K/Akt/mTOR pathway inhibitors in cancer: a perspective on clinical progress

Curr Med Chem. 2010;17(35):4326-41. doi: 10.2174/092986710793361234.

Abstract

The phosphoinositide 3-kinase (PI3K)/serine-theronine protein kinase Akt (also known as protein kinase B (PKB))/mammalian target of rapamycin (mTOR) pathway is a vital transduction cascade that is connected with many essential cellular activities, such as growth and survival. Along with extensive pharmacological studies validating the therapeutic potential of targeting the PI3K/Akt/mTOR pathway for the treatment of cancer, kinase inhibitors targeting significant knots of this pathway including PI3K, Akt, mTOR, and 3-phosphoinositide-dependent protein kinase-1 (PDK-1) keep arising and entering clinical studies. Herein, we review the most up-to-date landscape on developing small-molecule kinase inhibitors targeting the PI3K/Akt/mTOR pathway, with emphasis on small-molecule inhibitors which have been progressed into clinical studies.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Humans
  • Molecular Structure
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Structure-Activity Relationship
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Antineoplastic Agents
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt