Figure 5 from Combining Brigatinib with mTOR Inhibition to Effectively Treat NF2-SWN–Associated and Sporadic NF2-Deficient Meningiomas

AG-NF2-Men cells treated with the brigatinib + INK128 combination exhibited profoundly altered gene expression programs associated with growth suppression, including reduced expression of YAP target genes. A, Principal component analysis demonstrated that the biological triplicates from each treatment group clustered together. Groups separated by drug treatment are DMSO (brown), brigatinib (light blue), INK128 (orange), and brigatinib + INK128 (beige). B, Venn diagram showing that the brigatinib + INK128 combination–treated AG-NF2-Men cells exhibited 5,493 significant unique DEGs [P adj ≤ 0.01; antibodies (log2 FC) ≥ 1], whereas single agents only elicited a small number of DEGs. C, Tables showing a substantially larger number of upregulated and downregulated DEGs of all types (upper table) and of protein-coding genes (lower table) in the combination-treated cells compared with individual drug treatments. D, Volcano plots showing DEGs in AG-NF2-Men cells treated with brigatinib (left), INK128 (middle), and the brigatinib + INK128 combination (right) relative to the DMSO-treated controls. Downregulated genes are colored blue and upregulated genes are red, with the top 50 DEGs labeled. The YAP target genes ANKRD1, CTGF, CPA4, and CYR61 are circled. FC, fold change.