DC661 treatment in multiple melanoma cell lines (A375P, A375, WM35, and WM793) resulted in the activation of initiator caspase-8 and -9 and executioner caspase-7, typical for pyroptosis, and produced cleavage of full-length GSDME, similar in extent to the known pyroptosis inducer PLX4720 and PD0325901 (Supplemental Figure 5A). Here, CASP8 is linked to melanoma.