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While frequently amplified in cancers such as prostate and breast carcinoma\u2014where it drives oncogenesis via Wnt\/\u03b2\u2010catenin and PI3K\/AKT pathway activation\u2014emerging evidence positions TRIM24 as a tumor suppressor in specific contexts, modulating retinoic acid signaling and macrophage polarization. This dichotomy is governed by intricate post\u2010translational modifications (PTMs), including phosphorylation\u2010dependent nucleocytoplasmic shuttling and SUMOylation, which dictate substrate specificity for targets ranging from p53 to VHL. Furthermore, TRIM24 operates within a complex non\u2010coding RNA network (e.g., miRNA\u2010511, lncRNA NCK1\u2010AS1) that fine\u2010tunes its oncogenic output. Clinically, aberrant TRIM24 expression correlates with poor prognosis and therapeutic resistance across multiple malignancies. Mechanistically, its unique PHD\u2010Bromo dual\u2010domain structure confers specific recognition of the noncanonical H3K4me0\/H3K23ac histone signature, presenting a compelling therapeutic target. Current strategies, including PROTAC degraders and allosteric inhibitors targeting its bromodomain or downstream effectors (e.g., DNA\u2010PKcs, AURKB), demonstrate significant preclinical efficacy. This review synthesizes the molecular circuitry of TRIM24, elucidates the determinants of its functional switch, and evaluates emerging precision medicine approaches to overcome resistance in TRIM24\u2010addicted tumors.<\/jats:p>","DOI":"10.1002\/ijc.70565","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T10:50:43Z","timestamp":1781520643000},"page":"1602-1615","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>TRIM24<\/scp>\n                    in Human Cancers: A Dual\u2010Function Oncoprotein, Regulatory Mechanisms, and Emerging Therapeutic Strategies"],"prefix":"10.1002","volume":"159","author":[{"given":"Wenjie","family":"Zeng","sequence":"first","affiliation":[{"name":"Cancer Center, Department of Radiation Oncology Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College  Hangzhou Zhejiang China"},{"name":"School of Laboratory Medicine and Bioengineering, Hangzhou Medical College  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keke","family":"Xu","sequence":"additional","affiliation":[{"name":"Cancer Center, Department of Radiation Oncology Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuezhou","family":"Wang","sequence":"additional","affiliation":[{"name":"Cancer Center, Department of Radiation Oncology Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyi","family":"Shou","sequence":"additional","affiliation":[{"name":"Cancer Center, Department of Radiation Oncology Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Xiong","sequence":"additional","affiliation":[{"name":"Cancer Center, Department of Radiation Oncology Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanqing","family":"Liang","sequence":"additional","affiliation":[{"name":"College of Stomatology, Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong'en","family":"Xu","sequence":"additional","affiliation":[{"name":"Cancer Center, Department of Radiation Oncology Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Tongde Hospital of Zhejiang Province Affiliated to Zhejiang Chinese Medical University (Tongde Hospital of Zhejiang Province)  Hangzhou Zhejiang China"},{"name":"Zhejiang Academy of Traditional Chinese Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5134-4167","authenticated-orcid":false,"given":"Haibo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cancer Center, Department of Radiation Oncology Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwei","family":"Lu","sequence":"additional","affiliation":[{"name":"Cancer Center, Department of Radiation Oncology Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.107881"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.3310"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noaa138"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.51260"},{"issue":"24","key":"e_1_2_12_6_1","first-page":"10647","article-title":"TRIM24 Aggravates the Progression of Ovarian Cancer Through Negatively Regulating FOXM1 Level","volume":"23","author":"Zhou H. 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