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Cuproptosis in prostate cancer: Molecular mechanisms, prognostic biomarkers and therapeutic frontiers of cuproptosis‑related genes (Review)

  • Authors:
    • Zhugang Long
    • Yue Chang
    • Kun Zhu
    • Zhengyang Chen
    • Yaodong You
  • View Affiliations / Copyright

    Affiliations: Department of Urology/Andrology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, P.R. China, School of Clinical Medicine, Chengdu University of TCM, Chengdu, Sichuan 610075, P.R. China
    Copyright: © Long et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 77
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    Published online on: August 4, 2025
       https://doi.org/10.3892/ijo.2025.5783
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Abstract

Prostate cancer (PCa) is among the most prevalent malignancies in males globally and management remains complex. In recent years, cuproptosis, an emerging form of cell death, has offered novel insights for PCa treatment. Cuproptosis refers to a copper‑mediated cellular death mechanism that is intricately associated with mitochondrial metabolism, with cuproptosis‑related genes (CRGs) exerting a notable effect on both cuproptosis and PCa. CRGs and other cuproptosis‑associated indicators have demonstrated efficacy as prognostic predictors of PCa and these predictors may exhibit potential as novel therapeutic targets in the treatment of PCa. The mechanisms underlying cuproptosis in PCa remain to be fully elucidated; thus, further research is required to validate the expression patterns of CRGs and their associated indicators and examine the potential association with the characteristics, treatment responses and prognoses of patients with PCa. The present study aimed to investigate novel therapeutic strategies that may enhance the prognosis and quality of life of patients with PCa.
View Figures

Figure 1

Processes of copper metabolism and
cuproptosis. Cu2+ are reduced to Cu+ by
STEAP/DCYTB in the gut epithelium and transported into cells via
CTR1. Inside target cells, Cu+ interferes with Fe-S
clusters, generates ROS and leads to mitochondrial dysfunction.
Excess Cu+ induces protein aggregation via lipoylated
proteins, mediated by FDX1 and LIAS, ultimately causing
cuproptosis. STEAP, prostate six transmembrane epithelial antigen;
DCYTB, duodenal cytochrome b; CTR1, copper transporter 1;
TCA, tricarboxylic acid cycle; Fe-S, iron-sulfur; ROS, reactive
oxygen species; FDX1, ferredoxin 1; DLAT, dihydrolipoamide
S-acetyltransferase; LIAS, lipoic acid synthetase.

Figure 2

Dual mechanisms underlying copper and
cuproptosis in PCa. Mitochondrial dysfunction is central to
cuproptosis, leading to oxidative damage and inhibition of the TCA
cycle. Excess copper accumulation in mitochondria triggers
cuproptosis and sustained ROS production. Moderate ROS levels
promote DNA mutations and oncogenic signaling, driving tumor
progression. In contrast, excessive ROS overwhelm antioxidant
defenses and induce tumor cell death. The specific involvement in
PCa requires further validation. PCa, prostate cancer; TCA,
tricarboxylic acid cycle; ROS, reactive oxygen species.

Figure 3

Mechanism of copper ion carriers.
Elesclomol and disulfiram enhance intracellular Cu+
accumulation in tumor cells. In the presence of elevated lipoylated
proteins or ALDH expression (such as PCa), Cu+ induces
toxic stress within mitochondria, triggering cuproptosis and
resulting in tumor cell death. ALDH, acetaldehyde dehydrogenase;
PCa, prostate cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Long Z, Chang Y, Zhu K, Chen Z and You Y: Cuproptosis in prostate cancer: Molecular mechanisms, prognostic biomarkers and therapeutic frontiers of cuproptosis‑related genes (Review). Int J Oncol 67: 77, 2025.
APA
Long, Z., Chang, Y., Zhu, K., Chen, Z., & You, Y. (2025). Cuproptosis in prostate cancer: Molecular mechanisms, prognostic biomarkers and therapeutic frontiers of cuproptosis‑related genes (Review). International Journal of Oncology, 67, 77. https://doi.org/10.3892/ijo.2025.5783
MLA
Long, Z., Chang, Y., Zhu, K., Chen, Z., You, Y."Cuproptosis in prostate cancer: Molecular mechanisms, prognostic biomarkers and therapeutic frontiers of cuproptosis‑related genes (Review)". International Journal of Oncology 67.3 (2025): 77.
Chicago
Long, Z., Chang, Y., Zhu, K., Chen, Z., You, Y."Cuproptosis in prostate cancer: Molecular mechanisms, prognostic biomarkers and therapeutic frontiers of cuproptosis‑related genes (Review)". International Journal of Oncology 67, no. 3 (2025): 77. https://doi.org/10.3892/ijo.2025.5783
Copy and paste a formatted citation
x
Spandidos Publications style
Long Z, Chang Y, Zhu K, Chen Z and You Y: Cuproptosis in prostate cancer: Molecular mechanisms, prognostic biomarkers and therapeutic frontiers of cuproptosis‑related genes (Review). Int J Oncol 67: 77, 2025.
APA
Long, Z., Chang, Y., Zhu, K., Chen, Z., & You, Y. (2025). Cuproptosis in prostate cancer: Molecular mechanisms, prognostic biomarkers and therapeutic frontiers of cuproptosis‑related genes (Review). International Journal of Oncology, 67, 77. https://doi.org/10.3892/ijo.2025.5783
MLA
Long, Z., Chang, Y., Zhu, K., Chen, Z., You, Y."Cuproptosis in prostate cancer: Molecular mechanisms, prognostic biomarkers and therapeutic frontiers of cuproptosis‑related genes (Review)". International Journal of Oncology 67.3 (2025): 77.
Chicago
Long, Z., Chang, Y., Zhu, K., Chen, Z., You, Y."Cuproptosis in prostate cancer: Molecular mechanisms, prognostic biomarkers and therapeutic frontiers of cuproptosis‑related genes (Review)". International Journal of Oncology 67, no. 3 (2025): 77. https://doi.org/10.3892/ijo.2025.5783
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