CASP8 and cancer: Under normal conditions, TRAIL ligation with its death receptors (DR4 and DR5) on the surface of cancer cells induces the formation of the death-inducing signaling complex (DISC) involving Fas-associated death domain (FADD) recruitment of pro-caspase-8 via its death effector domain, resulting in caspase-8 or -10 activation, followed by cleavage and activation of caspase-3, -6, and -7, and eventual execution of apoptosis or anoikis.