Fig. 6

PI3K/AKT pathway and EZH2 as therapeutic targets for LUSC transformation. a In vivo tumor growth of the LUAD EGFR-mutant PDX model Lx462 with the EGFR inhibitor osimertinib, the EZH1/2 inhibitor ORS1, or their combination (N = 5 mice/treatment group). In vivo tumor growth of the squamous-like osimertinib-resistant EGFR-mutant PDX model Lx462 with the EGFR inhibitor osimertinib, the EZH1/2 inhibitor ORS1, or their combination (N = 6 mice/treatment group) (b); or with osimertinib, the AKT inhibitor samotolisib or their combination (N = 6 mice/treatment group) (c). For in vivo tumor growth, group mean tumor size ± SEM is shown. Statistical differences in tumor sizes were assessed by a two-tailed Student´s t-test, using the tumor sizes for osimertinib-treated group experiment endpoint. d Schematic summarizing the phenotypes and pathways altered upon LUSC transformation