{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Padrao N"],"funding":["Breast Cancer Ireland (BCI)","Cancer Research UK","European Research Council","Breast Cancer Now","KWF Kankerbestrijding (DCS)","ZonMw","Research Ireland"],"pagination":["e2507571122"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12377727"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["122(33)"],"pubmed_abstract":["While Estrogen receptor alpha (ERα)+ breast cancer treatment is considered effective, resistance to endocrine therapy is common. Since ERα is still the main driver in most therapy-resistant tumors, alternative therapeutic strategies are needed to disrupt ERα transcriptional activity. In this work, we position TRIM24 as a therapeutic target in endocrine resistance, given its role as a key component of the ERα transcriptional complex. TRIM24 interacts with ERα and other well-known ERα cofactors to facilitate ERα chromatin interactions and allows for maintenance of active histone marks including H3K23ac and H3K27ac. Consequently, genetic perturbation of TRIM24 abrogates ERα-driven transcriptional programs and reduces tumor cell proliferation capacity. Using a recently developed degrader targeting TRIM24, ERα-driven transcriptional output and growth were blocked, effectively treating not only endocrine-responsive cell lines but also drug-resistant derivatives thereof as well as cell line models bearing activating <i>ESR1</i> point mutations. Finally, using human tumor-derived organoid models, we could show the efficacy of TRIM24 degrader in the endocrine-responsive and -resistant setting. Overall, our study positions TRIM24 as a central component for the integrity and activity of the ERα transcriptional complex, with degradation-mediated perturbation of TRIM24 as a promising therapeutic avenue in the treatment of primary and endocrine resistance breast cancer."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["TRIM24 as a therapeutic target in endocrine treatment-resistant breast cancer."],"pmcid":["PMC12377727"],"funding_grant_id":["20/FFP-P/8597","813599","23/SPP/11783","18239A01","2019AugSF1310","016.156.401","2021JulyPCC1460","19/FFP/6443","2014MayPR234","C37/A18784","9171640"],"pubmed_authors":["Vareslija D","Padrao N","Siefert J","Severson TM","Buluwela L","Luzietti L","Gregoricchio S","Donaldson Collier M","Bossi D","Zwart W","Eickhoff N","Dong J","Ali S","Theurillat JP","Young L","Calcinotto A"],"additional_accession":[]},"is_claimable":false,"name":"TRIM24 as a therapeutic target in endocrine treatment-resistant breast cancer.","description":"While Estrogen receptor alpha (ERα)+ breast cancer treatment is considered effective, resistance to endocrine therapy is common. Since ERα is still the main driver in most therapy-resistant tumors, alternative therapeutic strategies are needed to disrupt ERα transcriptional activity. In this work, we position TRIM24 as a therapeutic target in endocrine resistance, given its role as a key component of the ERα transcriptional complex. TRIM24 interacts with ERα and other well-known ERα cofactors to facilitate ERα chromatin interactions and allows for maintenance of active histone marks including H3K23ac and H3K27ac. Consequently, genetic perturbation of TRIM24 abrogates ERα-driven transcriptional programs and reduces tumor cell proliferation capacity. Using a recently developed degrader targeting TRIM24, ERα-driven transcriptional output and growth were blocked, effectively treating not only endocrine-responsive cell lines but also drug-resistant derivatives thereof as well as cell line models bearing activating <i>ESR1</i> point mutations. Finally, using human tumor-derived organoid models, we could show the efficacy of TRIM24 degrader in the endocrine-responsive and -resistant setting. Overall, our study positions TRIM24 as a central component for the integrity and activity of the ERα transcriptional complex, with degradation-mediated perturbation of TRIM24 as a promising therapeutic avenue in the treatment of primary and endocrine resistance breast cancer.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-10T04:21:59.365Z","creation":"2026-04-08T01:29:08.821Z"},"accession":"S-EPMC12377727","cross_references":{"pubmed":["40815626"],"doi":["10.1073/pnas.2507571122"]}}