BBC3 and cancer: Bcl-xL blocks both extrinsic as well as intrinsic apoptosis upstream of mitochondrial outer membrane permeabilization by preventing action of pro-apoptotic BH3-only proteins involved in intrinsic apoptosis, for example, Bim, Puma, required for staurosporine or etoposide killing48, as well as Bid, connecting the mitochondrial pathway to death receptor-mediated apoptosis in many cancer cells after caspase-8-mediated proteolysis37.