TRAIL activates the death receptors DR4 and DR5. Obatoclax (GX) inhibits the protective BCL-2 family proteins BCL-XL and MCL-1. Sorafenib + HDAC inhibitor treatment has multiple targets; reduced expression of anti-apoptotic protein expression (FLIP, BCL-XL, MCL-1) and activation of BAX, BAD, BIM and NOXA. Thus [sorafenib + HDAC inhibitor] treatment facilitates TRAIL lethality by decreasing the levels of FLIP, BCL-XL, MCL-1 and activation of toxic BH3 domain proteins, whereas obatoclax can only facilitate the actions of [sorafenib + HDAC inhibitor] treatment on protective BCL-2 family proteins.