Targeting inhibitors of apoptosis increases sensitivity to ErbB antagonists. (a) BT474 cells and (b) MDAMB468 cells were transfected with siRNA targeting XIAP, and 24 hours later were treated with Trastuzumab (100 μg/ml), Lapatinib (100 nM), or Gefitinib (10 μM) for 48 hours. Apoptosis was scored, by examining nuclear morphology. Data presented as fold changes in apoptosis (mean ± standard error of the mean (SEM)) from at least three experiments. (c) BT474 cells were pretreated with the Smac mimetic for 2 hours before addition of Trastuzumab (100 μg/ml), Lapatinib (100 nM), or Gefitinib (10 μM). Cells were examined for nuclear morphology 48 hours later. Data presented as fold changes (mean ± SEM) from at least three experiments. (d) Cell turnover indexes (CTIs) for ErbB antagonist-treated BT474 cells in the presence or absence of XIAP depletion. Data presented as mean ± SEM from at least three experiments. *P values indicating significance. nt, not treated; con, no ErbB antagonist.