Fig. 5.

EGFR and CCNE1 amplifications could be potential biomarkers of therapy targeting EGFR and CDK2. a The efficacy of BK011 and cetuximab on five PDX models (n = 5 per group). Tumor volumes and proportion of tumor growth inhibition were expressed as means ± SD. NS, p > 0.05; ***p < 0.001 according to repeated measures ANOVA. CR, complete regression. b The immunohistochemical analysis of EGFR and phosphorylated EGFR expression in five PDX models. Scale bar represents 100 μm. c The expression and phosphorylation of EGFR, AKT, and S6 after BK011 or cetuximab treatment assessed by immunoblot. d CCNE1 copy numbers of eight PDX models quantified by real-time PCR and the tumor growth inhibition of AZD5438 in four PDX models. The copy number and proportion of tumor growth inhibition were expressed as means ± SD. NS, p > 0.05; ***p < 0.001 according to repeated measures ANOVA. e AZD5438 showed potent antiproliferative activity in two PDX models with CCNE1 copy numbers ≥ 29 alterations (n = 5 per group). Tumor volumes were expressed as means ± SD. NS, p > 0.05; ***p < 0.001 according to repeated measures ANOVA. f AZD5438 exerted antitumor effect in case 168 accompanied by reduction of expression of CDK2, CCNE1, and phosphorylated retinoblastoma (pRb). Whereas in case number 111, slight reduction of CDK2 but no impact on level of CCNE1 or pRB