Akt as a therapeutic target in cancer.
BACKGROUND
The phosphatidylinositol 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/v-akt murine thymoma viral oncogene homolog (Akt)/mammalian target of rapamycin (mTOR) pathway is central in the transmission of growth regulatory signals originating from cell surface receptors.


OBJECTIVE
This review discusses how mutations occur that result in elevated expression the PI3K/PTEN/Akt/mTOR pathway and lead to malignant transformation, and how effective targeting of this pathway may result in suppression of abnormal growth of cancer cells.


METHODS
We searched the literature for articles which dealt with altered expression of this pathway in various cancers including: hematopoietic, melanoma, non-small cell lung, pancreatic, endometrial and ovarian, breast, prostate and hepatocellular.


CONCLUSIONS
The PI3K/PTEN/Akt/mTOR pathway is frequently aberrantly regulated in various cancers and targeting this pathway with small molecule inhibitors and may result in novel, more effective anticancer therapies.
Steelman
Linda S
LS
Brody School of Medicine at East Carolina University, Department of Microbiology & Immunology, Greenville, NC 27858, USA.
Stadelman
Kristin M
KM
Chappell
William H
WH
Horn
Stefan
S
Bäsecke
Jörg
J
Cervello
Melchiorre
M
Nicoletti
Ferdinando
F
Libra
Massimo
M
Stivala
Franca
F
Martelli
Alberto M
AM
McCubrey
James A
JA
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D051057:Proto-Oncogene Proteins c-akt