Fig. 6: Targeting the AR and autophagy overcomes BRAFi resistance.

A375R and WM793R cells were treated with/without ARV110 (10 nM) and/or 3-MA (2.5 mM), A mRNA, B protein expression and C cell proliferation were measured as indicated. n = 3, two-tailed student’s t-test, ARV110 vs ARV110 + 3-MA in A375R **p = 0.0028, in WM793R **p = 0.0019. D Loewe additivity excess heatmap for A375R cells treated with the combination of AV110 and 3-MA. Darker coloration signifies enhanced cell killing and stronger synergistic interaction. A score >10 is considered significant. E Tumor-bearing nude mice were treated with PBS, ARV110 (10 mg/kg, qd), 3-MA (25 mg/kg, qd) or ARV110 (10 mg/kg) + 3-MA (25 mg/kg) as indicated, and representative images of dissected tumors at the end of the treatment period. F–H Quantitative analysis of Tumor weight, tumor volume and body weight in mice. I H&E staining of major organs from all groups of mice. Scale bar, 1 mm. J Protein expression in xenograft tumors as indicated. For F, G, Mean ± SEM; n = 4 mice. one-way ANOVA and Tukey’s post-hoc test, ns no significance, *p < 0.05, **p < 0.01, ***p < 0.001.