Inhibitors of phosphatidylinositol-3-kinase in cancer therapy

Mol Aspects Med. 2010 Apr;31(2):135-44. doi: 10.1016/j.mam.2010.02.003. Epub 2010 Feb 20.


The phosphatidylinositol-3-kinase (PI3K) signaling pathway is implicated in multiple aspects of tumorigenesis and tumor maintenance, and recent years have seen significant efforts towards developing agents to inhibit the pathway. However, the development of such agents raises issues such as what specific member or members in the PI3K family should be inhibited to achieve maximal therapeutic benefit, and can specific inhibitors be developed with the necessary pharmacologic properties to allow them to proceed to clinical trials? The number of PI3K inhibitors has gone from a handful of archetypal inhibitors which largely determined how the pathway was initially defined through their inhibition of PI3K, but also due to their off target properties, to a much larger number of inhibitors of not only PI3K but also other members of the PI3K family. The question remains to be answered whether greater therapeutic efficacy will be obtained through the use of inhibitors with increased specificity, or through inhibitors that target a spectrum of targets within the pathway. This review will cover the development of agents targeting the pathway, and will discuss current issues surrounding the development of such agents.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Phosphoinositide-3 Kinase Inhibitors*
  • Signal Transduction


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors