ArticleOncogene2022
Copper ionophore elesclomol selectively targets GNAQ/11-mutant uveal melanoma.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- The Hippo signalling pathway and its impact on eye diseases.Journal of cellular and molecular medicine · 2024Pooled it
- Elesclomol-mediated cuproptosis overcomes cisplatin resistance by restricting epigenetically activated mitochondrial respiration: Novel therapeutic insights into cisplatin-elesclomol combination therapy.Acta pharmaceutica Sinica. B · 2026Article
- Redox Homeostasis, Metabolic Pathways and Plasticity in Uveal Melanoma Compared to Other Cancers.Cancers · 2026Review
- Copper homeostasis and cuproptosis rewire the tumor microenvironment: mechanisms, immune modulation, and therapeutic opportunities.Journal of hematology & oncology · 2026Review
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Targeting Cuproptosis and Ferroptosis via a ROS-Responsive Nanoplatform for Enhanced Synergistic Therapy Against Hepatocellular Carcinoma.Antioxidants (Basel, Switzerland) · 2026Article
- Mitochondria-transliterated ALDH1L1 functions as a feedback regulator of redox homeostasis in cancer cells to enhance the resistance to pro-oxidative therapy.Cell death and differentiation · 2026Article
- Targeting mitochondrial homeostasis as a cancer treatment strategy: current status and future prospects.Molecular cancer · 2026Review
- Targeting mitochondria as a potential therapeutic strategy against radioresistance in cancer.Frontiers in oncology · 2026Review
- Elesclomol-Induced Copper Influx Attenuates Lung Adenocarcinoma Progression With Involvement of the ER Stress/PCK2 Axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Artemisinin synergizes with CCCP in autophagic cell death induction via ER stress in uveal melanoma.iScience · 2025Article
- [Research Progress on the Regulation of Third-generation EGFR-TKIs Resistance in Non-small Cell Lung Cancer by Redox Homeostasis].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- The molecular mechanism and therapeutic landscape of copper and cuproptosis in cancer.Signal transduction and targeted therapy · 2025Review
- Targeting cuproptosis for cancer therapy: Focus on the anti-tumor immune system.Cancer pathogenesis and therapy · 2025Review
- An up-To-Date Review of Elesclomol and Its Nano-Formulations in Cancer Therapy.Cancer reports (Hoboken, N.J.) · 2025Review
- Progress in Research on Regulated Cell Death in Cerebral Ischaemic Injury After Cardiac Arrest.Journal of cellular and molecular medicine · 2025Review
- Cuproptosis: a promising new target for breast cancer therapy.Cancer cell international · 2024Review
- Orchestrated copper-loaded nanoreactor for simultaneous induction of cuproptosis and immunotherapeutic intervention in colorectal cancer.Materials today. Bio · 2024Article
- Copper ions: The invisible killer of cardiovascular disease (Review).Molecular medicine reports · 2024Review
- Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives.Journal of hematology & oncology · 2024Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Unlike cutaneous melanoma, uveal melanoma (UM) is characterized by mutations in GNAQ and GNA11 and remains a fatal disease because there is essentially no effective targeted therapy or immunotherapy available. We report the discovery of the copper ionophore elesclomol as a GNAQ/11-specific UM inhibitor. Elesclomol was identified in a differential cytotoxicity screen of an in-house tool compound library, and its in vivo pharmacological efficacy was further confirmed in zebrafish and mouse UM models. Mechanistically, elesclomol transports copper to mitochondria and produces a large amount of reactive oxygen species (ROS) as Cu(II) is reduced to Cu(I) in GNAQ/11-mutant UM cells, which selectively activates LATS1 kinase in the Hippo signaling pathway and consequently promotes YAP phosphorylation and inhibits its nuclear accumulation. The inactivation of YAP downregulates the expression of SNAI2, which in turn suppresses the migration of UM cells. These findings were cross validated by our clinical observation that YAP activation was found specifically in UM samples with a GNAQ/11 mutation. Furthermore, addition of binimetinib, a MEK inhibitor, to elesclomol increased its synthetic lethality to GNAQ/11-mutant UM cells, thereby overriding drug resistance. This effect was confirmed in an orthotopic xenograft model and in a patient-derived xenograft model of UM. These studies reveal a novel mechanistic basis for repurposing elesclomol by showing that copper homeostasis is a GNAQ/11-specific vulnerability in UM. Elesclomol may provide a new therapeutic path for selectively targeting malignant GNAQ/11-mutant UM.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.