Fig. 6.

MAP3K1 and MAP2K4 mutant confer sensitivity to MEK inhibitor in vivo. a MDA-MB-468 cells were injected into nude mice. Once tumors reached 100 mm³, mice (six per group) were treated with vehicle, selumetinib (20 mg/kg/day), dacomitinib (3.75 mg/kg/day), or both drugs in combination (selumetinib 20 mg/kg/day + dacomitinib 3.75 mg/kg/day). The mean percentage change from the initial tumor volume is shown. Error bars represent standard error of the mean (SEM). b, c H358 b and HCT116 c cells, both Ctrl and MAP2K4 knockout cells, were injected into nude mice. Once tumors reach 100 mm³, mice (six per group) were treated with vehicle or selumetinib (20 mg/kg/day). The mean percentage change from the initial tumor volume is shown. Error bars represent standard error of the mean (SEM). d PDX drug response and mutation data were obtained from ref. ³⁶. Mutation data and binimetinib response data were available for 168 PDX models. Shown in the blue box plots is best average binimetinib response in 7 PDX tumors having either a MAP3K1 or a MAP2K4 mutation versus 161 without mutation in these genes; green box plots show tumor growth rate without drug. e Kaplan-Meier PFS curve of wild-type (n = 161) and MAP3K1 or MAP2K4 mutant (n = 7), untreated and binimetinib treated among the 168 PDX models. Numbers of animals at risk over time in each group is also shown