As evidenced in: hepatocellular carcinoma, where eIF2α phosphorylation triggers aberrant ISR activation, driving tumor progression and conferring therapy resistance (35); lung cancer, wherein chronic stress stimuli activate ISR through the HIF1A-AS3/HIF-1α axis, promoting tumorigenesis via macrophage reprogramming (36). The gene discussed is HIF1A; the disease is neoplasm.