CASP8 and cancer: This cancer cell-specific apoptotic response to TRAIL has yet to be successfully translated into a clinically efficacious therapeutic outcome because of the rapid onset of TRAIL resistance, which is attributed but not limited to TRAIL receptor mutation [3], increased expression of TRAIL decoy receptors DcR1 and DcR2 [4], decreased caspase-8 expression due to promoter hypermethylation [5], increased expression of c-FLIP that inhibits caspase-8 cleavage [6], increase expression of Bcl2 [7] or XIAP [7], and activation of the NF-kB pathway [8].