Syngeneic mice injected orthotopically with KPC 1203 cells were treated with vehicle, SHP099 (75 mg/kg q.d.), trametinib (0.25 mg/kg q.d.), or both drugs (trametinib 0.25 mg/kg q.d.; SHP099 75 mg/kg q.o.d.), as depicted in the scheme. Tumor mass was measured at days 15 and 25 (*, P < 0.05; **, P < 0.01; ***, P < 0.001, one-way ANOVA with Tukey multiple comparison test).