Targeting the Phosphoinositide 3-kinase Pathway in Cancer

Nat Rev Drug Discov. 2009 Aug;8(8):627-44. doi: 10.1038/nrd2926.

Abstract

The phosphoinositide 3-kinase (PI3K) pathway is a key signal transduction system that links oncogenes and multiple receptor classes to many essential cellular functions, and is perhaps the most commonly activated signalling pathway in human cancer. This pathway therefore presents both an opportunity and a challenge for cancer therapy. Even as inhibitors that target PI3K isoforms and other major nodes in the pathway, including AKT and mammalian target of rapamycin (mTOR), reach clinical trials, major issues remain. Here, we highlight recent progress that has been made in our understanding of the PI3K pathway and discuss the potential of and challenges for the development of therapeutic agents that target this pathway in cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Clinical Trials as Topic
  • Drug Delivery Systems
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Phosphoinositide-3 Kinase Inhibitors*
  • Protein Kinases / drug effects
  • Protein Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases

Substances

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