Targeting the PI3K/AKT pathway for the treatment of prostate cancer

Clin Cancer Res. 2009 Aug 1;15(15):4799-805. doi: 10.1158/1078-0432.CCR-08-0125. Epub 2009 Jul 28.

Abstract

Despite recent advances in our understanding of the biological basis of prostate cancer, the management of the disease, especially in the castration-resistant phase, remains a significant challenge. Deregulation of the phosphatidylinositol 3-kinase pathway is increasingly implicated in prostate carcinogenesis. In this review, we detail the role of this pathway in the pathogenesis of prostate cancer and the rapidly evolving therapeutic implications of targeting it. In particular, we highlight the importance of the appropriate selection of agents and combinations, and the critical role of predictive and pharmocodynamic biomarkers.

Publication types

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

MeSH terms

  • Androgen Receptor Antagonists
  • Chemokines / metabolism
  • Humans
  • Male
  • Oncogene Proteins, Fusion / metabolism
  • PTEN Phosphohydrolase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism*
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Receptors, Androgen / metabolism*
  • Serine Endopeptidases / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Trans-Activators / metabolism
  • Transcriptional Regulator ERG

Substances

  • Androgen Receptor Antagonists
  • Chemokines
  • ERG protein, human
  • Oncogene Proteins, Fusion
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Receptors, Androgen
  • TMPRSS2-ERG fusion protein, human
  • Trans-Activators
  • Transcriptional Regulator ERG
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Serine Endopeptidases
  • TMPRSS2 protein, human