Figure 6.

EZH2 inhibition in combination with zoledronic acid (ZA) limits tumor growth and prolongs survival of Bap1-deficient mesothelioma mice

(A and B) NSG mice with BNC and NC xenografts were treated with vehicle, ZA (0.1 mg/kg every other day), tazemetostat (250 mg/kg daily), or a combination. Shown is mean tumor volume over time (tumor volume ± SEM; n = 8 mice per treatment group). p value was determined by two-tailed unpaired Student’s t test; ∗p < 0.05, ∗∗p < 0.01.

(C) Schematic representation of experimental workflow of autochthonous Bap1-deficient mesothelioma mouse model.

(D) Kaplan-Meier curve comparing the survival of vehicle-, ZA-, tazemetostat-, and tazemetostat plus ZA-treated mice (n = 11 mice per treatment group). ZA was administered intraperitoneally once daily at 0.2 mg/kg. Tazemetostat was administered twice daily via oral gavage at 250 mg/kg. Dashed lines indicate start and end of treatment. The table depicts the median survival of each group. p value was determined by log rank (Mantel-Cox) test; ∗p < 0.05, ∗∗p < 0.01.

(E) A schematic summarizing the consequences of BAP1 loss in mesothelioma cells and their resulting sensitivities to PRC2 inhibitor (tazemetostat) and mevalonate pathway inhibitor (ZA).

See also Figure S6.