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. Author manuscript; available in PMC: 2023 Jun 15.
Published in final edited form as: Nature. 2022 Jun 15;606(7915):797–803. doi: 10.1038/s41586-022-04833-8

Figure 2: Treatment with BRAF/MEK inhibition is associated with increased AR expression and phenotype is recapitulated in preclinical models.

Figure 2:

b, AR staining in paired pre- and post-treatment male (blue) and female (pink) patient samples show increased AR expression in male samples (P = 0.01) but not in female patient samples (P = 0.21, two-sided t-test). c, AR staining post-treatment in male (n = 14, blue) and female (n = 9, pink) patients by MPR (P = 0.006, two-sided t-test). d, Androgen signalling score in patients achieving MPR (n = 11) versus <MPR (n = 11, P = 0.011, two-sided t-test). e, The percentage change in tumour volume in C57BL/6 mice that were implanted with YUMMER1.7 cells treated with vehicle or BRAF/MEK inhibition (BRAF/MEKi) (P = 0.031 male versus female BRAF/MEKi). n = 10 mice per group, aged 12–13 weeks. f, The percentage change in tumour volume in C57BL/6 mice implanted with Braf V600E Pten −/− mouse melanoma (BP) cells (P = 0.0006; male versus female BRAF/MEKi). Mice were treated as described in a. n = 10 mice per group, aged 12–13 weeks. The experiment was performed three times (Extended Data Fig. 3a,b). g, The percentage change in tumour volume in CD-1 nude mice that were implanted and treated as described in a (P = 0.004; male versus female BRAF/MEKi). n = 10 mice per group, aged 11 weeks. h, Aggregate end-point tumour volumes (n = 10 mice per study from five independent studies, P = 0.034, two-sided t-test). Individual points represent different studies. i, The percentage of cells with AR+ nuclei in YUMMER1.7 tumours in C57BL/6 mice that were treated with vehicle (n = 7 male and n = 7 female) or BRAF/MEKi (n = 7 female (P = 0.0006), n = 5 male (P = 0.0025), two-sided t-test) for 3 days. j, The percentage change in AR-KO BP tumour growth in CD-1 mice that were treated with vehicle or BRAF/MEKi (P = 0.76, male versus female BRAF/MEKi). n = 10 per group, aged 11 weeks. The tumour growth curves shown in e, f, g and j show mean ± s.e.m. and P values were computed using analysis of variance (ANOVA) with correction for multiple comparisons. The box plots in d and h show the median (centre line), interquartile range (IQR) (box limits) and the most extreme point within 1.5 × IQR (whiskers).