(A) Growth response curve of NCI-H1975 cells for osimertinib in the presence or absence of 0.1 mM phenformin (+Phen). (B) Growth response curve of NCI-H1975 cells for phenformin in the presence of absence of 160 nM osimertinib (+Osi). (C) Growth response curve of NCI-H1975, NCI-H1975-AZDR1 and NCI-H1975-AZDZR4 cells to phenformin. (D) Growth response curve to osimertinib of NCI-H1975, NCI-H1975-AZDR4, and NCI-H1975-AZDR4 cells co-treated with 0.1 mM phenformin. (E) Cells were treated for 24 h with 160 nM (PC9, PC9-GR6, PC9-VanR, HCC2935, HCC827, NCI-H1975) or 300 nM osimertinib alone or in combination with 300 nM selumetinib or 30 μM (PC9, PC9-GR6, PC9-VanR) or 0.1 mM phenformin and subjected to a caspase 3/7 assay as described in the Materials and Methods. Values shown are means relative to vehicle control +/− SEM (*p < 0.05; n ≥ 3). (F) Cells were treated for 24 h with either osimertinib (Osi; PC9 - 20 nM; NCI-H1975 – 160 nM), phenformin (PC9 – 30 μM; NCI-H1975 – 0.1 mM) or the combination of both. Cells were lysed and subjected to Western blotting.