In macrophages, for example, GSDME has been suggested to target mitochondria, promoting cytochrome c release to augment apoptosis.77 In cancer cell lines, the expression levels of GSDME play a role in deciding whether cells die by apoptosis or pyroptosis upon treatment with chemotherapeutic drugs, and consequently many cancer cell lines have downregulated GSDME expression.76 GSDME activation during apoptosis may contribute to the loss of membrane integrity in late apoptotic cells, a process known as secondary necrosis. This evidence concerns the gene CYCS and cancer.