CSIG-08: NITROSOUREAS IMPROVE SURVIVAL IN THE SECONDARY-LIKE AKT SUBTYPE OF GLIOBLASTOMA

The PI3K/AKT pathway regulates response to chemotherapeutics. We hypothesized this pathway varies between Glioblastoma (GB) patients and this effects response to therapeutics. We classified GB based on Akt pathway genes in a test set of tumors, and 5 Akt pathway subtypes resulted. The subtypes fit previous classifications, but further divided classes, yielding new subtypes with differing clinical and molecular features. We expanded this work into data sets within The Cancer Genome Atlas (TCGA), and investigated subtypes response to chemotherapeutics. We find one AKT subtype, called Secondary-Like, has a 4½ year survival advantage with nitrosourea treatment. This remained significant after correcting for age. This subtype has hallmarks of secondary GBM - younger age, longer survival and enrichment in IDH1 mutant and glioma CpG Island Methylator Phenotype (G-CIMP) tumors. We are currently validating these results in a second dataset and analyzing the contribution of the IDH1 and non-IDH1 mutant Secondary-Like tumors.