Fig. 1

FASN expression is associated with resistance to MAPKi therapy. a Melanoma biopsies were taken from patients that were treatment naïve, on MAPKi treatment, and following the development of therapy resistance. b FASN gene expression (RNAseq) in paired samples of human melanoma before or on MAPKi therapy, and at the onset of resistance as defined by a resurgence of tumor growth. Mixed-effects analysis. c-d Mel006 PDX tumor bearing mice were treated with DT. Tumors were harvested from treatment naïve (T0, n = 172), on MAKPi treatment mice (T4, n = 155; T28, n = 199), and following the development of therapy resistance as defined by the resurgence of tumor growth (Tres, n = 148). One-way ANOVA with Tukey’s multiple comparisons. e–f Single-cell RNA-seq analysis of KEGG fatty acid biosynthesis pathway and FASN gene expression in Mel006 PDX tumors, at T0, T4, T28 and Tres. One-way ANOVA with Tukey’s multiple comparisons. g Relative protein expression (western blotting) of FASN in MAPKi responsive (A375, 451lu) and resistant (451lu R, M233 and D10 BMR) cells (n = 3) following MAPKi inhibition. One-way ANOVA with Tukey’s multiple comparisons. Right panel shows a representative western blot experiment. Data represent mean ± SEM of biologically independent samples. (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001)