Targeting the PI3K/Akt/mTOR pathway--beyond rapalogs

Oncotarget. 2010 Nov;1(7):530-43. doi: 10.18632/oncotarget.101012.

Abstract

It is well established that the PI3K pathway plays a central role in various cellular processes that can contribute to the malignant phenotype. Accordingly, pharmacological inhibition of key nodes in this signaling cascade has been a focus in developmental therapeutics. To date, agents targeting upstream receptor tyrosine kinases are best studied and have achieved greatest clinical success. Further downstream, despite efficacy in certain tumor types, the rapalogs have been somewhat disappointing in the clinic. Novel inhibitors of PI3K, Akt, and mTORC1 and 2 are now passing through early phase clinical trials. It is hoped that these agents will circumvent some of the shortcomings of the rapalogs and lead to meaningful benefits for cancer patients.

Publication types

  • Evaluation Study
  • Review

MeSH terms

  • Animals
  • Humans
  • Models, Biological
  • Molecular Targeted Therapy / methods
  • Molecular Targeted Therapy / trends*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism

Substances

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