CASP8 and cancer: However, different mechanisms of intrinsic TRAIL resistance have also been observed in cancer cells, especially in melanoma.10,28 IZI1551-specific acquired resistance coincided with two major features, namely down-regulation of the initiator caspase-8 which is indispensable for downstream execution of apoptotic processes, and constitutive activation of the anti-apoptotic transcription factor NFκB.