Extended Data Fig. 4: Murine model of melanoma validates a sexually dimorphic response and suggests AR activity as a mechanism of resistance.

A-B) Percent change in tumour volume for male and female C57BL/6 mice implanted subcutaneously with BP cells that were treated with Vehicle or BRAF/MEKi (n = 10 mice per group; A – mice aged 9 weeks, B - mice aged 12 weeks). Results from the second and third repeats of this experiment are shown in A and B, respectively (p = 0.039 and p = 0.45). C) Percent change in tumour volume in BP injected C57BL/6 male mice treated with vehicle in the presence or absence of BRAF/MEKi with endocrine modulation through androgen blockade with enzalutamide or castration (mice aged 14 weeks). All tumour growth curves were compared by ANOVA with multiple comparisons (n = 10/group except BRAF/MEKi + castration where n = 9; p = 0.003 BRAF/MEKi vs BRAF/MEKi + Enzalutamide; p = 0.031 BRAF/MEKi vs BRAF/MEKi + Castration). D-E) Percent change in tumour volume for AR-KO BP tumours in female (D) (p = 0.99) and male (E) (p = 0.98) CD-1 mice treated with vehicle or BRAF/MEKi in combination with either testosterone or enzalutamide, respectively (n = 10 mice/group; aged 11 weeks). All tumour growth represented as mean + SEM and p-values were calculated using ANOVA with multiple comparisons.