1. AZD9291 inhibits EGFR phosphorylation and downstream signaling in murine models of EGFRT790M-resistant lung cancer.
AZD9291 inhibits EGFR phosphorylation and downstream signaling in murine models of EGFRT790M-resistant lung cancer. A, subcutaneous H1975 (L858R/T790M) xenografts, treated with a single 5 mg/kg dose of AZD9291 for the indicated times, were examined for phospho (p) EGFR, ERK, S6, and PRAS40 status by immunohistochemistry. Representative images were taken from scans at ×20 magnification and then size adjusted to fill the screen. B, lungs from representative transgenic mice treated with control, AZD9291, or afatinib were harvested 6 hours after dose administration. Formalin-fixed paraffin-embedded sections were stained with the indicated antibodies. Representative images were taken from Aperio scans at ×100 magnification. C, lungs were harvested from either untreated tumor-bearing transgenic mice (as confirmed by MRI; control) or from tumor-bearing mice 8 hours after a single treatment with AZD mg/kg. Corresponding lysates from individual animals were immunoblotted with the indicated antibodies. Anti–SP-C (surfactant protein C) antibody was used as a surrogate marker for tumor burden, as tumors express the protein.
Darren A.E. Cross et al. Cancer Discovery 2014;4:
©2014 by American Association for Cancer Research