We then found that response to TRAIL correlated significantly not only with caspase-8 cleavage (P=0.0086) but even with mitochondrial depolarization (P<0.0001, Figure 1b and Supplementary Table S1), in agreement with the notion that melanoma cells behave as type II cells in response to TRAIL, requiring activation of the intrinsic pathway of cell death.24 This latter finding provided also a mechanistic rationale for the co-targeting of oncogenic and death receptor pathways. This evidence concerns the gene CASP8 and melanoma.