ERBB2 and breast cancer: In a cell line model of HER2-overexpressing breast cancer, chronic exposure to the tyrosine kinase inhibitor (TKI) lapatinib (a dual-targeted quinazoline small-molecule inhibitor that reversibly binds to the cytoplasmic ATP-binding sites of EGFR/HER1 and HER2 receptors, thereby blocking tyrosine kinase enzymatic activity)41 led to development of acquired resistance mediated by increased ER signaling and a switch to co-dependency on ER and HER242.