ATF4 and neoplasm: Elevated ATF4 levels subsequently inhibit HSF1 activation, thereby diminishing the expression of HSF1-regulated genes This mechanism has been observed in human carcinoma cell lines and tumor xenograft models, where NXP800-induced ISR activation resulted in decreased HSF1 activity and reduced tumor cell proliferation (Cheeseman et al., 2017; Pasqua et al., 2023).