(A) SKOV3 xenografts were treated with vehicle, 2.5 mg/kg LBH589 (i.p.) daily, 0.25 mg/kg trametinib (i.p.) every other day, or the combination at the same doses (n = 8 per group). (B) Patient-derived xenograft PDX-POVC15 tumors implanted into NSG mice were randomized to untreated (control), 3.75 mg/kg LBH589 (i.p.) daily, 0.25 mg/kg trametinib (i.p.) every other day, or the combination at the same doses in each cohort (n = 8 per group). (C) Patient-derived xenograft PDX-POVC17 tumors implanted into NSG mice were randomized to untreated (control), 3.75 mg/kg LBH589 (i.p.) daily, 0.25 mg/kg trametinib (i.p.) every other day, or the combination at the same doses in each cohort (n = 4 per group). Data shown in A–C were plotted over time from the start of treatment (mean ± SEM). *P < 0.05, ***P < 0.001 by 2-way ANOVA with Tukey’s post hoc test. (D and E) Representative IHC (D) and quantification (E) of p-ERK1/2, Ki67, and DUSP6 in SKOV3 of experiments described in A. (F and G) Representative IHC (F) and quantification (G) of p-ERK1/2, Ki67, and DUSP6 in PDX-POVC15 of experiments described in B. (H and I) Representative IHC (H) and quantification (I) of p-ERK1/2, Ki67, and DUSP6 in PDX-POVC17 of experiments described in C. (D, F, and H) Scale bars: 50 μm. (E, G, and I) Quantification is shown from 3 tumors. *P < 0.05, **P < 0.01, ***P < 0.001 by 1-way ANOVA with Bonferroni’s post hoc test.