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
posted on 2023-03-30, 23:05authored byCatherine A. Eberlein, Daniel Stetson, Aleksandra A. Markovets, Katherine J. Al-Kadhimi, Zhongwu Lai, Paul R. Fisher, Catherine B. Meador, Paula Spitzler, Eiki Ichihara, Sarah J. Ross, Miika J. Ahdesmaki, Ambar Ahmed, Laura E. Ratcliffe, Elizabeth L. Christey O'Brien, Claire H. Barnes, Henry Brown, Paul D. Smith, Jonathan R. Dry, Garry Beran, Kenneth S. Thress, Brian Dougherty, William Pao, Darren A.E. Cross
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).