Core- and group-specific GSC SE genes pinpoint small-molecule inhibitors effective against GBM. (a) Integration of core GSC SE genes with the Washington University Drug Gene Interaction Database (Cotto et al., 2018) annotating 718 targets with small-molecule interactions (left) that could be classified into several drug classification categories (right). (b) In vitro treatment of GSC models harboring SEs regulating CDK6 with the CDK6 inhibitor palbociclib. (c) In vitro treatment of GSC models harboring SEs regulating EGFR with the EGFR inhibitor lapatinib. (d) In vivo drug treatment of the CW738 orthotopic xenograft GBM model with single or combinatorial agents palbociclib and lapatinib. (e) List and heatmap of drugs predicted to be GSC-group selective through integration with the Washington University Drug Gene Interaction Database (Cotto et al., 2018). (f) Depiction of the MAP3K1 locus harboring group 1 specific enhancer activity (left) and group 1–specific gene expression (right, two-sided Wilcoxon rank-sum test, P < 0.029). (g) Percentage of cell viability of group 1 and group 2 cells treated with the MAP3K1 inhibitor, AZD8330 at 0.78 μM. Cell proliferation experiments were performed in biological replicates with more than four technical replicates per time point. Error bars indicated as standard deviation of four technical replicates.