ERN1 and central nervous system cancer: In different settings, EGFR inhibition via gefitinib treatment in H4 and U87 glioma cells led to apparent ROS, free Ca2+ intracellular ion generation, and caspase-dependent apoptosis, mediated by global UPR activation and especially IRE1/Ask/JNK upregulation, in parallel with decreased MAPK/Akt signaling (Figure 3).