First of all, if cells can successfully impose restrictions on pro-apoptotic UPR outputs, IRE1 and PERK signaling pathways will facilitate the survival and growth of cancer cells under hypoxia and nutrient deprivation in vivo (Koumenis et al., 2002; Romero-Ramirez et al., 2004; Chen et al., 2014). This evidence concerns the gene EIF2AK3 and cancer.