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.
Keywords: AKT, PKB, glioblastoma, inhibitors, brain cancer, cancer therapy, chemotherapy, autophagy, apoptosis, antibiotic
Current Pharmaceutical Design
Title: Targeting the AKT Pathway in Glioblastoma
Volume: 17 Issue: 23
Author(s): Kelli A. McDowell, Gregory J. Riggins and Gary L. Gallia
Affiliation:
Keywords: AKT, PKB, glioblastoma, inhibitors, brain cancer, cancer therapy, chemotherapy, autophagy, apoptosis, antibiotic
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.
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Cite this article as:
A. McDowell Kelli, J. Riggins Gregory and L. Gallia Gary, Targeting the AKT Pathway in Glioblastoma, Current Pharmaceutical Design 2011; 17 (23) . https://dx.doi.org/10.2174/138161211797249224
DOI https://dx.doi.org/10.2174/138161211797249224 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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