Figure 5.

Determinants of GBM vulnerability to inhibitors of NEDD8 activating enzyme (NAE). Four PTEN WT (GBM12, 15, 38, and 43), 2 PTEN DEL (GBM120 and 102) and 5 PTEN MUT (GBM10, 39, 76, 116, and 108) lines were treated with MLN4924, TAS4464, or Candesartan Cilexetic (CDC) for 72 hours. (A) Sensitivity ranking of 11 GBM patient-derived xenograft (PDX) cultures to each of 3 different NAE inhibitors. (B) The average ranking of drug response in each group of PTENwt, PTENdel, and PTENmut. Unsupervised hierarchical clustering of (C) Mayo PDX models and (D) 17 Cancer Cell Line Encyclopedia (CCLE) glioma cell lines based on gene sets (Gene set names in Supplementary Table. Fig 5) demonstrated to be significantly differentially expressed between GBM cell lines that were sensitive and resistant to MLN4924 (Figure 2). (E) PCA plot of 17 CCLE lines using the NAEi Response Gene Set.