2008•Expert Opinion on Therapeutic TargetsRequires access
Akt as a therapeutic target in cancer
Linda S. Steelman, Kristin M. Stadelman, William H. Chappell, Stefan Horn, Jörg Bäsecke, Melchiorre Cervello, Ferdinando Nicoletti, Massimo Libra, Franca Stivala, Alberto M. Martelli, James A. McCubrey
Open publisher page 140 citations
Abstract
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. RESULTS/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.