ERBB2 and breast carcinoma: However, upon persistent treatments malignant cells may acquire the ability to disrupt this process by altering the pH of the lysosomal compartment to slow the catabolic activity of their proteases, a process that has been demonstrated in HER2-positive breast cancer clones resistant to long-term T-DM1 (Ríos-Luci et al., 2017; García-Alonso et al., 2018).