Targeting the AKT pathway in glioblastoma

Kelli A. Mcdowell, Gregory J Riggins, Gary L Gallia

Research output: Contribution to journalArticle

Abstract

Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. The treatment options for patients diagnosed with GBM are limited and the current median survival is 14-16 months following diagnosis. Genetic mutations have been identified that act as drivers of GBM growth and these should be considered as a basis for identifying novel therapeutic strategies. AKT is a downstream serine/threonine kinase in the RTK/PTEN/PI3K pathway and large scale genomic analysis of GBM has demonstrated that this pathway is mutated in the majority of GBMs. This RTK/PTEN/PI3K pathway leads to activated AKT and phospho-AKT levels are elevated in the majority of GBM tumor samples and cell lines, which studies show help glioma cells grow uncontrolled, evade apoptosis, and enhance tumor invasion. AKT represents a nodal point in this pathway which allows for amplification of growth signals, thereby making inhibition of AKT an attractive target for GBM therapy. Many different classes of AKT inhibitors exist, however, few have been tested sufficiently to demonstrate in vivo efficacy. This article will summarize the key components of the Akt pathway with special attention to gliomas, the genetic alterations driving this pathway in gliomas, and the studies evaluating inhibitors of this pathway. Inhibitors of the Akt pathway represent a potential treatment option against GBM and additional research efforts are required to fully explore and develop this possible treatment strategy.

Original languageEnglish (US)
Pages (from-to)2411-2420
Number of pages10
JournalCurrent Pharmaceutical Design
Volume17
Issue number23
DOIs
StatePublished - Aug 2011

Fingerprint

Glioblastoma
Glioma
Phosphatidylinositol 3-Kinases
Therapeutics
Protein-Serine-Threonine Kinases
Growth
Tumor Cell Line
Brain Neoplasms
Apoptosis
Mutation
Survival
Research
Neoplasms

Keywords

  • Akt
  • Brain cancer
  • Cancer therapy
  • Glioblastoma
  • Inhibitors
  • Pkb

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

Cite this

Targeting the AKT pathway in glioblastoma. / Mcdowell, Kelli A.; Riggins, Gregory J; Gallia, Gary L.

In: Current Pharmaceutical Design, Vol. 17, No. 23, 08.2011, p. 2411-2420.

Research output: Contribution to journalArticle

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