{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Singh S"],"funding":["NIAID NIH HHS","NCI NIH HHS"],"pagination":["eabq2096"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9548378"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(653)"],"pubmed_abstract":["Chimeric transcription factors drive lineage-specific oncogenesis but are notoriously difficult to target. Alveolar rhabdomyosarcoma (RMS) is an aggressive childhood soft tissue sarcoma transformed by the pathognomonic Paired Box 3-Forkhead Box O1 (PAX3-FOXO1) fusion protein, which governs a core regulatory circuitry transcription factor network. Here, we show that the histone lysine demethylase 4B (KDM4B) is a therapeutic vulnerability for PAX3-FOXO1<sup>+</sup> RMS. Genetic and pharmacologic inhibition of KDM4B substantially delayed tumor growth. Suppression of KDM4 proteins inhibited the expression of core oncogenic transcription factors and caused epigenetic alterations of PAX3-FOXO1-governed superenhancers. Combining KDM4 inhibition with cytotoxic chemotherapy led to tumor regression "],"journal":["Science translational medicine"],"pubmed_title":["Targeting KDM4 for treating PAX3-FOXO1-driven alveolar rhabdomyosarcoma."],"pmcid":["PMC9548378"],"funding_grant_id":["P30 CA021765","K08 CA255569","P01 CA196539","R03 CA212802","R01 CA229739","R01 CA247941","R21 CA227926","R01 AI114581","R01 AI175004"],"pubmed_authors":["Young B","Fang J","Lewis PW","Guo Y","Wu Q","Vaithiyalingam S","Murphy AJ","Abu-Zaid A","Wu G","Rankovic Z","Yun MK","Davidoff AM","Honnell V","Jin H","Pruett-Miller SM","Shao Y","Wang R","Hatley M","Xu B","Wang T","White SW","Bowling J","Chen X","Singh S","Chen EY","Quarni W","Maxham L","Chen T","Yang J","Tan H","Fan Y","Easton J","Grosveld GC","Li Y","Feng H","Abdolvahabi A","Bajpai R","Peng J"],"additional_accession":[]},"is_claimable":false,"name":"Targeting KDM4 for treating PAX3-FOXO1-driven alveolar rhabdomyosarcoma.","description":"Chimeric transcription factors drive lineage-specific oncogenesis but are notoriously difficult to target. Alveolar rhabdomyosarcoma (RMS) is an aggressive childhood soft tissue sarcoma transformed by the pathognomonic Paired Box 3-Forkhead Box O1 (PAX3-FOXO1) fusion protein, which governs a core regulatory circuitry transcription factor network. Here, we show that the histone lysine demethylase 4B (KDM4B) is a therapeutic vulnerability for PAX3-FOXO1<sup>+</sup> RMS. Genetic and pharmacologic inhibition of KDM4B substantially delayed tumor growth. Suppression of KDM4 proteins inhibited the expression of core oncogenic transcription factors and caused epigenetic alterations of PAX3-FOXO1-governed superenhancers. Combining KDM4 inhibition with cytotoxic chemotherapy led to tumor regression ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2026-05-28T06:11:30.552Z","creation":"2025-04-05T23:32:27.868Z"},"accession":"S-EPMC9548378","cross_references":{"pubmed":["35857643"],"doi":["10.1126/scitranslmed.abq2096"]}}