CASP8 and cancer: To date no auto-activating mutants of FADD or caspase-8 have been identified in disease, this is likely due to their propensity to trigger apoptosis, however, somatic loss of function mutants or repression of expression of FADD and caspase-8 are associated with numerous cancers, and seem to drive NF-κB (Teitz et al., 2000; Shin et al., 2002; Kim et al., 2003; Tourneur et al., 2004; Soung et al., 2005; Ando et al., 2013).