T-DXd has also been shown to have a cytotoxic effect on proximate non-HER2-expressing cells in the tumor microenvironment, possibly due to the membrane permeability of deruxtecan and/or the presence of cathepsins in the tumor microenvironment that catalyze extracellular linker cleavage (Shiraishi et al., 2025, Kepp and Kroemer, 2025). This evidence concerns the gene CTSS and neoplasm.