Phosphatidylinositol 3-kinase inhibitors: promising drug candidates for cancer therapy

Cancer Sci. 2008 Sep;99(9):1734-40. doi: 10.1111/j.1349-7006.2008.00891.x. Epub 2008 Jul 4.


Phosphatidylinositol 3-kinases (PI3K) are a group of lipid kinases that phosphorylate phosphoinositides at the 3-hydroxyl group of the inositol ring to generate phosphatidylinositol 3,4,5-trisphosphate, a second messenger with key roles in fundamental cellular responses such as cell proliferation and metabolism. Frequent mutations found in or amplification of the PIK3CA gene and loss of phosphatase and tensin homolog deleted on chromosome 10 function in human tumors suggest that PI3K is a potential target for cancer therapy. During the last 5 years, several specific PI3K inhibitors were developed that were directed against various diseases. Some of them revealed potent anticancer efficacy and are now undergoing clinical trials. Some PI3K inhibitors showed antiangiogenic effects. Combined use of PI3K inhibitors with other chemotherapeutic agents or with radiotherapy produced synergistic therapeutic efficacies in treating cancer and showed reduced side effects. The rapid progress made in developing novel PI3K inhibitors in recent years promises bright prospects for finding a PI3K-targeted anticancer drug in the near future.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Androstadienes / pharmacology
  • Androstadienes / therapeutic use
  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Proliferation / drug effects*
  • Chromones / pharmacology
  • Chromones / therapeutic use
  • Combined Modality Therapy
  • Humans
  • Morpholines / pharmacology
  • Morpholines / therapeutic use
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Isoforms
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Wortmannin


  • Androstadienes
  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Chromones
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Isoforms
  • Protein Kinase Inhibitors
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Wortmannin