Fig. 2

Effect of FGFR1-3 inhibitor AZD4547 on the KCC_P_4043 PDX model. a Effect on tumor growth. Mice were treated with vehicle control or AZD4547 for short term (5 d; 4 mice per group) or long term (28 d; 10 mice per group) and the tumor volume measured daily. Statistical significance for short-term treatment group was determined using the two-way ANOVA test (p value = 0.0425). Statistical significance for long-term treatment group was determined by unpaired t test at Day 14 (p value < 0.001). Tumor weight at endpoint for the short-term treatment group was also determined, with statistical significance determined by unpaired t test. b Effect on cell proliferation. FFPE tumor sections from the short-term treatment group were stained for Ki67 and quantified. Statistical significance was determined using the unpaired t test. c Effects on site-selective protein phosphorylation as determined by MS-based phosphoproteomics. Data from phosphotyrosine- and TiO2-enrichment workflows are presented, highlighting phosphosites downregulated in response to AZD4547. d Effects on downstream signaling determined by Western blotting. Lysates were Western blotted as indicated. Phosphorylated AKT and ERK were quantified by densitometry. Data were first normalized relative to the tubulin control, then phosphorylated proteins normalized to the total protein and expressed relative to the average of the vehicle control which was arbitrarily set at 1.0. Mouse 1 of the AZD4547 treatment group was excluded from this analysis due to ineffective drug delivery. Statistical significance was determined by unpaired t test. * indicates p value of < 0.05, ** < 0.01. Error bars: mean ± standard error of biological replicates