GBM response to Smo and PI3K inhibitors

Combination therapy with Smo and PI3K inhibitors results in a synergistic effect in reducing tumor growth in PTEN-deficient Glioblastoma. To identify consequences of combination therapy with an Smo inhibitor and a PI3K inhibitor on a genome-wide scale, we performed Affymetrix microarrays with two different PTEN-deficient GBMs treated with single drugs or combination therapy. A small set of genes was significantly affected by combination therapy in hBT70 and/or hBT112, including several genes implicated in GBM prognosis, or identified as targets of Shh, PI3K or S6 pathways 29-33 . There are two different human GBM tumors (BT70 and BT112). Both are PTEN deficient. Samples were treated with DMSO (Control), LDE225 at 1 uM for 5 days, BKM 120 100 nM for 5 days, or LDE225 1 uM and BKM 120 100 nM for 5 days (Combo). Two biological replicates of each condition were analyzed.