Another mechanism that is commonly involved in induction of necrosis is generation of ROS.47 Indeed, HDAC inhibitors can kill cells by the production of ROS independently of caspase activation.56, 57 However, although ROS were produced in BRAFV600E melanoma cells by treatment with SAHA in combination with PLX4720, they did not appear to be involved in induction of necrosis as the antioxidant GSH was unable to prevent the cells from death. The gene discussed is HDAC9; the disease is melanoma.