Moreover, whilst downregulation of cFLIP and Mcl-1 readily occurred in caspase-8-deficient cancer cells, absence of caspase-8 completely prevented the TRAIL-dependent appearance of pro-apoptotic tBid, cleaved poly-ADP ribose polymerase (PARP) and cleaved caspase-3 which rendered these cells resistant to apoptosis induction by TRAIL–CDK9i (Fig. 5c-d). This evidence concerns the gene CASP8 and cancer.