The PI3K/AKT Pathway as a Target for Cancer Treatment

Annu Rev Med. 2016;67:11-28. doi: 10.1146/annurev-med-062913-051343. Epub 2015 Oct 14.

Abstract

Anticancer targeted therapies are designed to exploit a particular vulnerability in the tumor, which in most cases results from its dependence on an oncogene and/or loss of a tumor suppressor. Genes in the phosphoinositide 3-kinase (PI3K)/AKT pathway are the most frequently altered in human cancers. Aberrant activation of this pathway, as a result of these somatic alterations, is associated with cellular transformation, tumorigenesis, cancer progression, and drug resistance. Several drugs targeting PI3K/ATK are currently in clinical trials, alone or in combination, in both solid tumors and hematologic malignancies. These drugs are the focus of this review.

Keywords: breast cancer; lymphoproliferative disorders; mammalian target of rapamycin (mTOR); mutation; pathway inhibitors; phosphoinositide 3-kinase (PI3K)/AKT.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Female
  • Humans
  • Lymphoproliferative Disorders / drug therapy
  • Molecular Targeted Therapy / methods*
  • Phosphatidylinositol 3-Kinase / genetics
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, ErbB-2 / analysis
  • Receptors, Estrogen / analysis
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Antineoplastic Agents
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Receptors, Estrogen
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Phosphatidylinositol 3-Kinase
  • ERBB2 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • Proto-Oncogene Proteins c-akt