ArticleOncotarget2016
Copper as a target for prostate cancer therapeutics: copper-ionophore pharmacology and altering systemic copper distribution.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- Cuproptosis: Mechanisms, biological significance, and advances in disease treatment-A systematic review.CNS neuroscience & therapeutics · 2024Pooled it
- Review
- Development and validation of a cuproptosis-immune prognostic signature for risk stratification and personalized therapy in cutaneous melanoma.Discover oncology · 2026Article
- Copper isotope fractionation and copper-to-zinc ratios reveal altered metal homeostasis in prostate cancer.Scientific reports · 2026Article
- Review
- Copper Complexes: Main Mechanisms as Anticancer Agents.Molecules (Basel, Switzerland) · 2026Review
- Tackling cuproptosis: from metabolic rewiring to therapeutic exploitation in cancer.Cellular & molecular immunology · 2026Review
- Cuproptosis in prostate cancer: Molecular mechanisms, prognostic biomarkers and therapeutic frontiers of cuproptosis‑related genes (Review).International journal of oncology · 2025Review
- Copper-Based Nanotubes That Enhance Starvation Therapy Through Cuproptosis for Synergistic Cancer Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cuproptosis and its potential role in musculoskeletal disease.Frontiers in cell and developmental biology · 2025Review
- Construction of a cuproptosis‑related lncRNA signature to predict biochemical recurrence of prostate cancer.Oncology letters · 2024Article
- Copper and Colorectal Cancer.Cancers · 2024Review
- The antibacterial activity of the copper forHeliyon · 2024Article
- Enzalutamide Sensitizes Castration-Resistant Prostate Cancer to Copper-Mediated Cell Death.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- ATPase Copper Transporting Beta (ATP7B) Is a Novel Target for Improving the Therapeutic Efficacy of Docetaxel by Disulfiram/Copper in Human Prostate Cancer.Molecular cancer therapeutics · 2024Article
- Cuproptosis: Unraveling the Mechanisms of Copper-Induced Cell Death and Its Implication in Cancer Therapy.Cancers · 2024Review
- The role of metal ions in the occurrence, progression, drug resistance, and biological characteristics of gastric cancer.Frontiers in pharmacology · 2024Review
- Research progress on cuproptosis in cancer.Frontiers in pharmacology · 2024Review
- Copper in Gynecological Diseases.International journal of molecular sciences · 2023Review
- The promise of copper ionophores as antimicrobials.Current opinion in microbiology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Copper-ionophores that elevate intracellular bioavailable copper display significant therapeutic utility against prostate cancer cells in vitro and in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice. However, the pharmacological basis for their anticancer activity remains unclear, despite impending clinical trails. Herein we show that intracellular copper levels in prostate cancer, evaluated in vitro and across disease progression in TRAMP mice, were not correlative with copper-ionophore activity and mirrored the normal levels observed in patient prostatectomy tissues (Gleason Score 7 & 9). TRAMP adenocarcinoma cells harbored markedly elevated oxidative stress and diminished glutathione (GSH)-mediated antioxidant capacity, which together conferred selective sensitivity to prooxidant ionophoric copper. Copper-ionophore treatments [CuII(gtsm), disulfiram & clioquinol] generated toxic levels of reactive oxygen species (ROS) in TRAMP adenocarcinoma cells, but not in normal mouse prostate epithelial cells (PrECs). Our results provide a basis for the pharmacological activity of copper-ionophores and suggest they are amendable for treatment of patients with prostate cancer. Additionally, recent in vitro and mouse xenograft studies have suggested an increased copper requirement by prostate cancer cells. We demonstrated that prostate adenocarcinoma development in TRAMP mice requires a functional supply of copper and is significantly impeded by altered systemic copper distribution. The presence of a mutant copper-transporting Atp7b protein (tx mutation: A4066G/Met1356Val) in TRAMP mice changed copper-integration into serum and caused a remarkable reduction in prostate cancer burden (64% reduction) and disease severity (grade), abrogating adenocarcinoma development. Implications for current clinical trials are discussed.
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Registered trials
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.