Fig. 5
Pathway analysis of co-therapeutics to increase sensitivity to vemurafenib. (a) CausalPath results for protein causal relationships that are significantly up- or down-regulated in vemurafenib resistant cells (FDR = 0.2). (b) Heatmap of z-score normalized expression of ErbB family receptors and related downstream signaling proteins. Top heatmap indicates training set and bottom indicates testing set of cell lines in order of increasing IC50 AUC, with dotted line separating between AUC < 0.2. (c) Weights of all receptors in RPPA receptor-only O-PLS model. (d) VIP scores of receptors in RPPA receptor-only O-PLS model. (e) Comparison of IC50 AUC for vemurafenib monotherapy and predicted IC50 AUC for dual therapy with vemurafenib and a pan-ErbB inhibitor in MDA-MB-361, LS411N, and A375 cell lines. (f) Impact of dual pan-ErbB and BRAF inhibition using dacomitinib and vemurafenib in MDA-MB-361, LS411N, and A375 cell lines. + indicates the measured dose that was closest to the IC50 for dual treated. (g) Comparison of effects of dual treatment near the IC50 and the component monotherapies of vemurafenib (V) and dacotinib (D) for each cell line