Supplementary Figures S1-S6 from Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models

Supplementary Figures S1-S6. Comparison of genetic alterations across multiple populations resistant to AZD9291 and other EGFR TKIs (S1); Treatment of resistant populations with AZD9291 (S2); Detection and Validation of a novel NRAS E63K mutation (S3); Lysates were prepared from parental PC9 and resistant populations analysed for levels of total and phosphorylated ERK, NRAS and KRAS by western blot (S4); The novel NRAS E63K mutation is an activating mutation that when expressed enhances resistance to cell growth inhibition by gefitinib or AZD9291 in EGFRm cell lines (S5); In vitro combination of AZD9291 with selumetinib induces more profound phenotype inhibition (S6).