Dual blockade with antibody–drug conjugate and targeted therapy. (A) SCID Beige mice were injected with 1 million cells per mouse in the estrogen receptor-positive, human epidermal growth factor receptor (HER)-positive cell line called BT474-m1. These animals were randomized into six groups and treated with: vehicle control; trastuzumab (5 mg/kg once weekly); lapatinib (100 mg/kg daily); ado-trastuzumab-emtansine (TDM-1; 5 mg/kg weekly); trastuzumab (5 mg/kg once weekly) + lapatinib (100 mg/kg daily); or TDM-1 (5 mg/kg weekly) + lapatinib (100 mg/kg daily). Tumor volume fold-change will be measured twice weekly post treatment. (B), (C) BT474 and SKBR3 HER2-positive cell lines were treated with the following: vehicle control; TDM-1 (1 μg/ml); trastuzumab (10 μg/ml) + lapatinib (10 μM) 4); or TDM-1 (1 μg/ml) + lapatinib (10 μM). Cells were assessed for proliferation and apoptosis post treatment. *Data analyzed by one way analysis of variance followed by Tukey analysis for a pairwise comparison of different groups, P < 0.05. T, trastuzumab; L, lapatinib. Data from J Chang, unpublished data.