Fig. 7: Treatment of glioblastoma harboring EGFR G598V mutation with dacomitinib.

a PC9 cell lines expressing either LacZ, EGFR WT, EGFR T790M, EGFR VKS extracellular domain variants (R108K, M277E, A289V, or G598V) after 144 h treatment with increasing doses of dacomitinib (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. b Colony formation with PC9 EGFR mutants and controls as in (a) after 10 d of treatment with either vehicle (DMSO), 50 nM, or 100 nM dacomitinib. A representative experiment is shown (N = 3). c, d Representative immunoblots displaying the effect of 10 nM dacomitinib after 24 h treatment on PC9 EGFR mutants and controls as in (a) on the levels of both phosphorylated EGFR and ERK and total EGFR and ERK. β-actin immunoblotting was used to determine equivalent loading (c). Total levels of phosphorylated-EGFR or ERK were normalized to total levels of either EGFR or ERK. Data are presented as mean values ± SEM of biological replicates (N = 3) (d). e Images of an EGFR G598V positive glioblastoma patient after treatment with dacomitinib. f, g EGFR extracellular domain mutations observed in lung cancer patients from Dana-Farber Cancer Institute (f) or Moffit Cancer Center (g) based on z-score enrichment from the screen.