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Although primary UM can be effectively controlled, a significant proportion of cases (40% or more) eventually develop distant metastases, commonly in the liver. Metastatic UM remains a lethal disease with limited treatment options. The initiation of UM is typically attributed to activating mutations in <jats:italic>GNAQ<\/jats:italic> or <jats:italic>GNA11<\/jats:italic>. The elucidation of the downstream pathways such as PKC\/MAPK, PI3K\/AKT\/mTOR, and Hippo\u2010YAP have provided potential therapeutic targets. Concurrent mutations in BRCA1 associated protein 1 (<jats:italic>BAP1<\/jats:italic>) or splicing factor 3b subunit 1 (<jats:italic>SF3B1<\/jats:italic>) are considered crucial for the acquisition of malignant potential. Furthermore, in preclinical studies, actionable targets associated with BAP1 loss or oncogenic mutant SF3B1 have been identified, offering promising avenues for UM treatment. This review aims to summarize the emerging targeted and epigenetic therapeutic strategies for metastatic UM carrying specific driver mutations and the potential of combining these approaches with immunotherapy, with particular focus on those in upcoming or ongoing clinical trials.<\/jats:p>","DOI":"10.1111\/pcmr.13161","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T11:35:33Z","timestamp":1709033733000},"page":"411-425","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Emerging therapeutic strategies for metastatic uveal melanoma: Targeting driver mutations"],"prefix":"10.1111","volume":"37","author":[{"given":"Xiao\u2010lian","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Run\u2010hua","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010xuan","family":"Pan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010jie","family":"Li","sequence":"additional","affiliation":[{"name":"Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010lei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10615"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15030886"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/2767\u20109764.CRC\u201022\u20100399"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2006.02.007"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006982\u2010200402000\u201000001"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2020.38.15_suppl.10036"},{"key":"e_1_2_11_8_1","unstructured":"Carlino M. 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