Status of PI3K inhibition and biomarker development in cancer therapeutics

Ann Oncol. 2010 Apr;21(4):683-691. doi: 10.1093/annonc/mdp347. Epub 2009 Aug 27.


The phosphatidylinositol 3-kinase (PI3K) signalling pathway is integral to diverse cellular functions, including cellular proliferation, differentiation and survival. The 'phosphate and tensin homologue deleted from chromosome 10' (PTEN) tumor suppressor gene plays a critical role as a negative regulator of this pathway. An array of genetic mutations and amplifications has been described affecting key components of this pathway, with implications not only for tumorigenesis but also for resistance to some classic cytotoxics and targeted agents. Emerging preclinical research has significantly advanced our understanding of the PI3K pathway and its complex machinations and interactions. This knowledge has enabled the evolution of rationally designed drugs targeting elements of this pathway. It is important that the development of suitable biomarkers continues in parallel to optimize use of these agents. A new generation of PI3K inhibitors is now entering early clinical trials, with much anticipation that they will add to the growing armamentarium of targeted cancer therapeutics.

Publication types

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

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Pharmacological / analysis*
  • Biomarkers, Pharmacological / metabolism
  • Clinical Trials as Topic
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Models, Biological
  • Mutation / physiology
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Oncogene Protein v-akt / antagonists & inhibitors
  • Oncogene Protein v-akt / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics


  • Antineoplastic Agents
  • Biomarkers, Pharmacological
  • Enzyme Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors
  • Oncogene Protein v-akt