ERBB2 and neoplasm: (1) reduced HER2 expression, reduced T-DM1 binding, dysregulated PI3K signaling, signaling through alternative RTKs, and the tumor immune set point; (2) intratumor heterogeneity in HER2 expression and accessibility; (3) altered internalization of HER2–T-DM1 complexes; (4) impaired lysosomal release of lysine-MCC-DM1