Lapatinib combination with MEK or PI3K inhibitors induces synergistic growth inhibition in HER2-L755S mutant cells. (a and b) Cell proliferation of indicated MCF10A cells treated with lapatinib (5uM for L755S, 350nM for WT and del.16), AZD6244 (1uM for L755S, 400nM for WT and del.16), or in combination as indicated. Representative data are expressed as log2-fold change normalized to day 0 of three technical replicates. (c) Western blotting showing the expression of HER2, EGFR, MEK1/2 and p42/44 MAPK in MCF10A bearing HER2-L755S treated with MEK inhibitor AZD6244 (1uM) and lapatinib (1uM) for 24 h. (d and e) Cell proliferation of indicated MCF10A cells treated with lapatinib (5uM for L755S, 350nM for WT and del.16), GDC0941 (1uM for L755S, WT and del.16), or in combination as indicated. Representative data are expressed as log2-fold change normalized to day 0 of three technical replicates. (F) Western blotting showing the expression of HER2, EGFR, AKT and p70S6K in MCF10A bearing HER2-L755S treated with PI3K inhibitor GDC0941 (1uM) and/or lapatinib (1uM) for 24 h.