Abstract 1049: Akt1 and Akt2 are associated with poor outcome in glioblastoma multiforme

Abstract The Akt pathway is implicated in progression of astrocytic tumors. To refine the Akt pathway as a therapeutic target in glioblastoma multiforme (GBM) we determined activated Akt isoform(s) that mediate cellular behavior, and are associated with clinical parameters. Akt1 and Akt2 message is associated with worse clinical outcome while Akt3v1 message is associated with better clinical outcome. Silencing individual isoforms with shRNA gives different phenotypes. Bioinformatic analysis indicates that PI3K/Akt pathway components cluster with individual Akt isoforms and with tumor subtype suggesting that different arms of the PI3K/Akt pathway are associated with individual isoforms. Taken together, the data indicate that Akt3 function differs from Akt1 and 2 function, and support a role for Akt1 and 2 in the malignant behavior of glioma cells. Selective inhibition of Akt1 and/or 2, or their downstream effectors may be more effective and less toxic than general inhibition of Akt or PI3K. Supported by the Barrow Neurological Foundation (AJ and BGF). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1049.