{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T06:59:18Z","timestamp":1785135558015,"version":"3.55.0"},"reference-count":198,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: To date there is a lack of an integrative review literature on redox homeostasis, oxidative stress and the influence on metabolic pathways and plasticity in uveal melanoma (UM), since most literature findings are from cutaneous melanoma (CM), a genetically and behaviorally distinct cancer. Furthermore, UM metabolic pathway comparison to other cancers could provide more insight into metastatic UM, a difficult-to-treat malignancy. Methods: A wide-ranging multi-step literature search of PubMed and Web of Science for redox balance, oxidative stress, antioxidants and metabolic plasticity in UM, with expanded search terms for connections with other cancers. Results: UM cells maintain redox homeostasis via several redox loops: glutathione, thioredoxin, peroxiredoxins, peroxisomal catalase and the mitochondrial antioxidative network. NADPH plays a key role in regenerating UM antioxidative capabilities. Key redox signaling pathways are the subject of ongoing research in UM: NRF2 signaling, AMPK, mTOR, MAPK, FoxO. These pathways are less studied versus CM and present behavior differences in UM. PON2, studied in CM, represents a literature gap in UM. Inside the tumoral microenvironment, UM presents high metabolic plasticity and easy switching from glycolysis to oxidative phosphorylation (OXPHOS). Thus, UM eschews the classic Warburg effect loop and instead presents high oxidative phosphorylation (OXPHOS) gene expression, which generates additional lactate, which in turn produces cascade reprogramming in the metabolic pathways and lactate metabolism particularities associated in experimental studies with immune-escape phenomena. Uveal melanoma\u2019s OXPHOS capabilities confer survival advantages and subdivide tumoral populations into OXPHOS-high and OXPHOS-low variants. Glycolysis\/OXPHOS metabolic plasticity is an ongoing research field in other cancers with common and different elements vs. UM: cutaneous melanoma, small cell lung carcinoma, pancreatic cancer, breast cancer, acute myeloid leukemia, prostate cancer, renal cell carcinoma and glioblastoma. Uveal melanoma cells are susceptible to deleterious effects of prooxidants, a metabolic vulnerability which helps to create genetic pleomorphism, selecting higher proliferation and dissemination variants. Conclusions: Uveal melanoma is an oncogenic mutation and mitochondrial metabolism-driven malignancy, with metabolic connections to other malignancies. Emerging understanding of redox homeostasis, redox pathway signaling, mitochondrial oxidative and oncogenic metabolism could lead to better understanding of therapeutic response and new therapeutic targets. This review novelly integrates the general and CM redox literature with the UM literature, painting a complex redox signaling and metabolic plasticity picture of UM.<\/jats:p>","DOI":"10.3390\/cancers18152402","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:49:27Z","timestamp":1785131367000},"page":"2402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Redox Homeostasis, Metabolic Pathways and Plasticity in Uveal Melanoma Compared to Other Cancers"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6000-1118","authenticated-orcid":false,"given":"Mihai Adrian","family":"P\u0103s\u0103ric\u0103","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Clinical Institute for Ophthalmological Emergencies \u201cProf. Dr. Mircea Olteanu\u201d, 010464 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9487-2832","authenticated-orcid":false,"given":"Paul Filip","family":"Curc\u0103","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Central Military Emergency University Hospital \u201cDr. Carol Davila\u201d, Carol Davila University of Medicine and Pharmacy, 010825 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiana Diana Maria","family":"Dragosloveanu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Clinical Institute for Ophthalmological Emergencies \u201cProf. Dr. Mircea Olteanu\u201d, 010464 Bucharest, Romania"},{"name":"Department of Ophthalmology, Clinical Institute for Ophthalmological Emergencies \u201cProf. Dr. Mircea Olteanu\u201d, Carol Davila University of Medicine and Pharmacy, 010464 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosmin Ionu\u021b","family":"Nisipa\u0219u","sequence":"additional","affiliation":[{"name":"Department of Dental Medicine I, Implant-Prosthetic Therapy, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3708-3597","authenticated-orcid":false,"given":"George Cristian","family":"Curc\u0103","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine and Bioethics, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"ref_1","unstructured":"Kumar, V. 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