FIGURE 1 from Combined Inhibition of EZH2 and FGFR is Synergistic in BAP1-deficient Malignant Mesothelioma

Combined FGFR and EZH2 inhibition reveals strong synergy in BAP1-deficient mesothelioma. A, 3D synergy plots visualizing the synergy score for the different concentrations and combinations of FGFR and EZH2 inhibitors in Bap1-proficient (NC) and Bap1-deficient (BNC) mouse mesothelioma cells. Shown are the results of three independent replicates. B, 3D synergy plots visualizing the synergy score for the different concentrations and combinations of the inhibitors in BAP1-proficient (NCI-H2810) and BAP1-deficient (NCI-H2731) human mesothelioma cell lines. Shown are the results of three independent replicates. C, Similar to the data shown in A, the clinically available inhibitor tazemetostat was used as an EZH2 inhibitor instead of GSK126. D, Similar to the data shown in B, the clinically available inhibitor tazemetostat was used as an EZH2 inhibitor instead of GSK126. E, Long-term clonogenicity assays of mouse mesothelioma cell lines treated with DMSO, GSK126 (7.5 µmol/L), AZD4547 (0.75 µmol/L), or the combination. F, Long-term clonogenicity assays of human mesothelioma cell lines treated with DMSO, GSK126 (7.5 µmol/L), AZD4547 (0.75 µmol/L), or the combination. Representative images are shown from three independent experiments. Quantification data are mean ± SEM, n = 3 independent experiments. Representative images are shown from three independent experiments. Quantification data are mean ± SEM, n = 3 independent experiments. G, Similar to the data shown in E, the clinically available inhibitor tazemetostat (10 µmol/L) was used as an EZH2 inhibitor instead of GSK126. H, Similar to the data shown in F, the clinically available inhibitor tazemetostat (10 µmol/L) was used as an EZH2 inhibitor instead of GSK126; images of control wells are duplicated for presentation purposes, P values were determined by using two-tailed unpaired Student t test; ∗, P ∗∗, P ∗∗∗, P ∗∗∗∗, P < 0.0001.