biostudies-literatureWu KNCRR NIH HHSNCI NIH HHSNIH HHSNIGMS NIH HHS487-495https://www.ebi.ac.uk/biostudies/studies/S-EPMC12779550biostudies-literatureUnknown649(8096)Emerging evidence indicates that cancer cells are susceptible to ferroptosis, a form of cell death that is triggered by uncontrolled lipid peroxidation^1-3. Despite broad enthusiasm about harnessing ferroptosis as a novel anti-cancer strategy, whether ferroptosis is a barrier to tumorigenesis and can be leveraged therapeutically remains unknown^4,5. Here, using genetically engineered mouse models of lung adenocarcinoma, we performed tumour-specific loss-of-function studies of two key ferroptosis suppressors, GPX4^6,7 and ferroptosis suppressor protein 1 (FSP1)^8,9, and observed increased lipid peroxidation and robust suppression of tumorigenesis, suggesting that lung tumours are highly sensitive to ferroptosis. Furthermore, across multiple pre-clinicNatureTargeting FSP1 triggers ferroptosis in lung cancer.PMC12779550S10 RR027926P30 CA016087R01 CA262562R37 CA222504T32 GM136573S10 OD021747R01 CA227649S10 OD032292T32 GM136542R01 CA283049F30 CA275258Wu KPapagiannakopoulos TBossowski JPChung SPillai RHan MSimeone DHao YConrad MZiogou AWang LKim THNakamura MNVaughan AJMancini MRajalingam SNakamura TShackelford DKim SMKang YPfalseTargeting FSP1 triggers ferroptosis in lung cancer.Emerging evidence indicates that cancer cells are susceptible to ferroptosis, a form of cell death that is triggered by uncontrolled lipid peroxidation^1-3. Despite broad enthusiasm about harnessing ferroptosis as a novel anti-cancer strategy, whether ferroptosis is a barrier to tumorigenesis and can be leveraged therapeutically remains unknown^4,5. Here, using genetically engineered mouse models of lung adenocarcinoma, we performed tumour-specific loss-of-function studies of two key ferroptosis suppressors, GPX4^6,7 and ferroptosis suppressor protein 1 (FSP1)^8,9, and observed increased lipid peroxidation and robust suppression of tumorigenesis, suggesting that lung tumours are highly sensitive to ferroptosis. Furthermore, across multiple pre-clinic2026-01-01T00:00:00Z2026 Jan2026-06-06T12:54:56.098Z2026-05-30T03:11:38.886ZS-EPMC127795504119380010.1038/s41586-025-09710-8