ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Enzalutamide Sensitizes Castration-Resistant Prostate Cancer to Copper-Mediated Cell Death.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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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.
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Who cites it
35 citing papers in PubMed.
- Tumor‑immune spatiotemporal co‑evolution: A new paradigm for understanding and overcoming therapy resistance in metastatic castration‑resistant prostate cancer (Review).International journal of molecular medicine · 2026Review
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- DLST Succinylation-Mediated Mitochondrial Metabolic Remodeling and Cuproptosis Resistance Promote Malignant Progression of Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- EP300-Mediated MTF1-K218 Lactylation Buffers AR-Driven Copper Overload to Suppress Cuproptosis in Castration-Resistant Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Copper homeostasis and cuproptosis rewire the tumor microenvironment: mechanisms, immune modulation, and therapeutic opportunities.Journal of hematology & oncology · 2026Review
- From copper imbalance to immunometabolic remodeling: cuproptosis-related vulnerability and therapeutic hypotheses in autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Role of Ferredoxin 1Cancer pathogenesis and therapy · 2026Review
- Review
- Copper-EGCG nanoreactor orchestrates dual-metabolic assault and self-amplified cuproptosis for immunogenic prostate cancer therapy.Journal of nanobiotechnology · 2026Article
- Biobank of genetically defined murine prostate cancer tumoroids uncovers oncogenic pathways and drug vulnerabilities driven by PTEN-loss.Cell reports methods · 2026Article
- Research Progress on Elesclomol-Induced Cuproptosis for Antitumor Effects.Biomedicines · 2026Review
- Tackling cuproptosis: from metabolic rewiring to therapeutic exploitation in cancer.Cellular & molecular immunology · 2026Review
- PDHA1-acetylation signaling suppresses cuproptosis to attenuate anti-androgen effect in prostate cancer.Cell death & disease · 2026Article
- Harnessing Cuproptosis resistance to advance cancer therapeutics.Apoptosis : an international journal on programmed cell death · 2026Review
- Cuproptosis and prostate cancer: from molecular mechanisms and microenvironment remodeling to precision therapy.Frontiers in oncology · 2026Review
- Mitochondrial convergence of ferroptosis and cuproptosis in castration-resistant prostate cancer: From metabolic vulnerabilities to therapeutic targeting.BBA advances · 2026Review
- High TERF2 expression is associated with poor prognosis and its suppression attenuates progression in acute myeloid leukemia.Translational cancer research · 2025Article
- FAM111B promotes prostate cancer progression by inhibiting apoptosis via ATF3 suppression and MAPK pathway activation: a novel biomarker and therapeutic target.Cancer cell international · 2025Article
- Unraveling the miR-144-3p/PUMA pathway: a novel regulator of FDX1-mediated cuproptosis in colorectal cancer.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Copper death combination therapy: the innovative frontier and challenges in prostate cancer treatment.Cancer biology & therapy · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Despite the initial efficacy of enzalutamide in castration-resistant prostate cancer (CRPC), inevitable resistance remains a significant challenge. Here, the synergistic induction of copper-dependent cell death (cuproptosis) in CRPC cells is reported by enzalutamide and copper ionophores (elesclomol/disulfiram). Mechanistically, enzalutamide treatment increases mitochondrial dependence in CRPC cells, rendering them susceptible to cuproptosis, as evidenced by specific reversal with the copper chelator tetrathiomolybdate. This susceptibility is characterized by hallmarks of cuproptosis, including lipoylated protein aggregation and iron-sulfur cluster protein instability. Interestingly, the mitochondrial matrix reductase, FDX1, specifically correlates with elesclomol sensitivity, suggesting a potential mechanistic divergence between the two copper ionophores. Notably, this synergistic effect extends beyond in vitro models, demonstrating efficacy in 22Rv1 xenografts, mouse Pten p53 knockout organoids. Importantly, enzalutamide significantly enhances copper ionophore-mediated cytotoxicity in enzalutamide-resistant cells. Collectively, these findings indicate that enzalutamide and copper ionophores synergistically induce cuproptosis, offering a promising therapeutic avenue for CRPC, potentially including enzalutamide-resistant cases.
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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.