biostudies-literatureLi JNIDCD NIH HHS22382https://www.ebi.ac.uk/biostudies/studies/S-EPMC11437005biostudies-literatureUnknown14(1)Cisplatin is a commonly used chemotherapy agent with a nearly universal side effect of sensorineural hearing loss. The cellular mechanisms underlying cisplatin ototoxicity are poorly understood. Efforts in drug development to prevent or reverse cisplatin ototoxicity have largely focused on pathways of oxidative stress and apoptosis. An effective treatment for cisplatin ototoxicity, sodium thiosulfate (STS), while beneficial when used in standard risk hepatoblastoma, is associated with reduced survival in disseminated pediatric malignancy, highlighting the need for more specific drugs without potential tumor protective effects. The unfolded protein response (UPR) and endoplasmic reticulum (ER) stress pathways have been shown to be involved in the pathogenesis of noise-induced hearing loss aScientific reportsModulating the unfolded protein response with ISRIB mitigates cisplatin ototoxicity.PMC11437005DC018583-01R01 DC018583Rouse SLLi JPark YMatthews IREltawil YChan DKSherr EHfalseModulating the unfolded protein response with ISRIB mitigates cisplatin ototoxicity.Cisplatin is a commonly used chemotherapy agent with a nearly universal side effect of sensorineural hearing loss. The cellular mechanisms underlying cisplatin ototoxicity are poorly understood. Efforts in drug development to prevent or reverse cisplatin ototoxicity have largely focused on pathways of oxidative stress and apoptosis. An effective treatment for cisplatin ototoxicity, sodium thiosulfate (STS), while beneficial when used in standard risk hepatoblastoma, is associated with reduced survival in disseminated pediatric malignancy, highlighting the need for more specific drugs without potential tumor protective effects. The unfolded protein response (UPR) and endoplasmic reticulum (ER) stress pathways have been shown to be involved in the pathogenesis of noise-induced hearing loss a2024-01-01T00:00:00Z2024 Sep2025-04-03T23:49:56.511Z2025-04-03T23:49:56.511ZS-EPMC114370053933323510.1038/s41598-024-70561-w