ERBB2 and breast cancer: However, the role of caveolin-mediated endocytosis in T-DM1 resistance is contentious as, in the same study, shRNA-mediated knockdown of caveolin-1 (CAV1) was insufficient to re-sensitise resistant NCI-N87 cells to T-DM1.28 Furthermore, Chung et al.53,54 reported opposing findings: overexpression of CAV1 in BT-474 breast cancer cells or upregulation through pre-treatment with trastuzumab or metformin increased T-DM1 sensitivity, while siRNA-mediated CAV1 knockdown in HER2-positive SK-BR-3 cells reduced sensitivity.