Fig. 6: EGFR extracellular domain variant sensitivity to afatinib and dacomitinib.
From: Comprehensive mutational scanning of EGFR reveals TKI sensitivities of extracellular domain mutants
a Domain schematic and ribbon structure of EGFR extracellular domain variants of unknown significance (VUS). b, c PC9 cell lines expressing either LacZ, EGFR WT, EGFR T790M, EGFR extracellular domain variants (R222C, S229C, A237Y, T302H, C311R, S447F, C595G, or P644S) after 144 h treatment with increasing doses of afatinib (b) or dacomitinib (c) (normalized to vehicle control). A representative experiment is shown, remaining biological replicates are located in Source Data (N = 3). Data are presented as mean values ± SD. d, e Colony formation with PC9 EGFR mutants and controls as in (b) and (c) after 10 d of treatment with either vehicle (DMSO), 10 nM (d) or 50 nM (e) of either afatinib or dacomitinib. A representative experiment is shown (N = 3). f–i Representative immunoblots displaying the effect of either afatinib (f, h) or dacominitib (g, i) after 24 h treatment on PC9 EGFR mutants and controls as in (b) and (c) on the levels of both phosphorylated EGFR and ERK and total EGFR and ERK. β-actin immunoblotting was used to determine equivalent loading.
