In 2006 we demonstrated that the primary mechanism by which AR-12 killed tumor cells was via the PKR-like endoplasmic reticulum kinase (PERK)-dependent induction of endoplasmic reticulum stress signaling and a toxic form of autophagy which through mitochondrial dysfunction with the release of both cytochrome c and AIF and a necroptotic form of cell death [3]. This evidence concerns the gene EIF2AK3 and neoplasm.