EIF2AK3 and cancer: In eukaryotic cells, the aberrant accumulation of unfolded or misfolded proteins at the endoplasmic reticulum (ER) induces ER stress, which is emerging as a possible driver of human cancers and contributes to resistance to chemotherapy, target therapy and immunotherapy.44–46 EIF2S1, also known as EIF2α, plays a key role in the PERK-EIF2α signaling, which is one of three major ER stress branches.