PI3K/Akt/mTOR signaling pathway and targeted therapy for glioblastoma

Oncotarget. 2016 May 31;7(22):33440-50. doi: 10.18632/oncotarget.7961.

Abstract

Glioblastoma multiform (GBM) is the most common malignant glioma of all the brain tumors and currently effective treatment options are still lacking. GBM is frequently accompanied with overexpression and/or mutation of epidermal growth factor receptor (EGFR), which subsequently leads to activation of many downstream signal pathways such as phosphatidylinositol 3-kinase (PI3K)/Akt/rapamycin-sensitive mTOR-complex (mTOR) pathway. Here we explored the reason why inhibition of the pathway may serve as a compelling therapeutic target for the disease, and provided an update data of EFGR and PI3K/Akt/mTOR inhibitors in clinical trials.

Keywords: EGFR; PI3K/Akt/mTOR pathway; glioblastoma; targeted therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Glioblastoma / drug therapy*
  • Glioblastoma / enzymology
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Humans
  • Molecular Targeted Therapy*
  • 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 / metabolism
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism
  • Treatment Outcome

Substances

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