The drug OSU-03012 (AR12) was originally thought to act as an anti-cancer agent by inhibiting the enzyme PDK-1 within the PI3K pathway however it was subsequently shown that this compound was not primarily acting as a PDK-1 inhibitor, and subsequently it was 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. This evidence concerns the gene EIF2AK3 and neoplasm.