Linked Life Data

16305480

Source:http://linkedlifedata.com/resource/pubmed/id/16305480

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-11-24
pubmed:abstractText
The phosphatidylinositol 3-kinase (PI3K)/Akt (protein kinase B, PKB) signaling pathway plays a critical role in cell growth and survival. Dysregulation of this pathway has been found in a variety of cancer cells. Recently, constitutively active PI3K/Akt signaling has been firmly established as a major determinant for cell growth and survival in an array of cancers. Blocking the constitutively active PI3K/AKT signaling pathway provides a new strategy for targeted cancer therapy. Thus, inhibitors of this signaling pathway would be potential anticancer agents, particularly for cancer cells whose survival and growth are dominated by constitutively active PI3K/Akt signaling. This review describes the current understanding of small molecule drugs targeting this pathway both in vitro and in vivo. Inhibitors and functions of the upstream and downstream molecular targets of the PI3K/Akt pathway are discussed in the context of using the inhibitors to block this pathway for targeted cancer therapy. Special emphasis is placed on the following targets: receptor tyrosine kinases, PI3K, Akt, and the mammalian target of rapamycin. While the molecular therapeutic strategy holds great promise for the treatment of a variety of cancers, few small molecule inhibitors with potential high therapeutic indexes are available. Thus, new inhibitors with high selectivity, bioavailability, and potency are greatly needed. Novel approaches toward the development of PI3K/Akt pathway inhibitors as anticancer therapeutics are discussed in detail, with emphasis on chemical genetics-based and structure-based drug design.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1568-0118
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
575-89
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Inhibition of PI3K/Akt signaling: an emerging paradigm for targeted cancer therapy.
pubmed:affiliation
Department of Pharmacology, the University of Minnesota Medical School, Minneapolis, MN 55455, USA. chenx112@umn.edu
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural