PMID- 21827416
OWN - NLM
STAT- MEDLINE
DCOM- 20120522
LR  - 20220317
IS  - 1873-4286 (Electronic)
IS  - 1381-6128 (Linking)
VI  - 17
IP  - 23
DP  - 2011
TI  - Targeting the AKT pathway in glioblastoma.
PG  - 2411-20
AB  - 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.
FAU - McDowell, Kelli A
AU  - McDowell KA
AD  - Ludwig Collaborative Laboratory, Department of Neurosurgery, Johns Hopkins 
      University School of Medicine, Baltimore, MD 21231, USA.
FAU - Riggins, Gregory J
AU  - Riggins GJ
FAU - Gallia, Gary L
AU  - Gallia GL
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United Arab Emirates
TA  - Curr Pharm Des
JT  - Current pharmaceutical design
JID - 9602487
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Isoforms)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology/*therapeutic use
MH  - Brain Neoplasms/*drug therapy/enzymology/genetics/pathology
MH  - Clinical Trials as Topic
MH  - Drug Screening Assays, Antitumor
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology/*therapeutic use
MH  - Glioblastoma/*drug therapy/enzymology/genetics/pathology
MH  - Humans
MH  - Phosphatidylinositol 3-Kinases/genetics
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Isoforms
MH  - Proto-Oncogene Proteins c-akt/*antagonists & inhibitors/genetics
MH  - Signal Transduction/*drug effects
MH  - Treatment Outcome
EDAT- 2011/08/11 06:00
MHDA- 2012/05/23 06:00
CRDT- 2011/08/11 06:00
PHST- 2011/06/27 00:00 [received]
PHST- 2011/07/26 00:00 [accepted]
PHST- 2011/08/11 06:00 [entrez]
PHST- 2011/08/11 06:00 [pubmed]
PHST- 2012/05/23 06:00 [medline]
AID - BSP/CPD/E-Pub/000553 [pii]
AID - 10.2174/138161211797249224 [doi]
PST - ppublish
SO  - Curr Pharm Des. 2011;17(23):2411-20. doi: 10.2174/138161211797249224.