On the other hand, cathepsins can be secreted out of the cells, in particular in cancer cells.22 A study recently found that extracellular release of cathepsin L in HER2 low breast cancer cells enables cleavage of T-DXds linker and subsequent payload release.28 This T-DXd-dependent cytotoxicity is not related to cellular uptake and would therefore not be reliant on the quantity of antigen expression on the cell surface. This evidence concerns the gene CTSS and breast cancer.