REVIEW article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1555858
This article is part of the Research TopicRenewed Insight into Cancer Mechanism and TherapyView all 34 articles
Copper metabolism and cuproptosis: Broad perspectives in the treatment of hepatocellular carcinoma
Provisionally accepted
- 1广西中医药大学附属瑞康医院, 南宁市, China
- 2广西中医药大学, 南宁市, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Copper is an essential trace element that plays a pivotal role in multiple biological processes, including energy production and angiogenesis. It is also a vital cofactor necessary for the maintenance of biological functions and has been implicated in cancer development. The recently identified form of cell death, cuproptosis, has a unique induction mechanism—accumulated copper ions directly bind to lipoylated proteins in the mitochondrial tricarboxylic acid (TCA) cycle, triggering toxic protein aggregation and cell death. This process can be specifically induced by oxidative stress and mitochondrial dysfunction, providing a novel direction for the development of anti-tumor strategies that target copper metabolism. In hepatocellular carcinoma (HCC), there is a significant correlation between disturbances in copper metabolism and abnormalities in the cuproptosis pathway. HCC cells maintain pro-carcinogenic copper levels through the upregulation of copper transporter proteins such as copper transporter 1 (CTR1). Conversely, the dysregulation of the expression of key genes involved in cuproptosis (ferredoxin 1, lipoic acid synthetase) may mediate treatment resistance. In this review, we focus on the mechanism by which cuproptosis influences the occurrence and development of HCC, evaluate its potential as a diagnostic biomarker, and examine therapeutic strategies targeting this form of cell death (nanocarrier-based delivery of copper ion carriers, CRISPR-mediated editing of copper-regulated genes). These strategies may provide a novel perspective for overcoming the current therapeutic limitations of HCC.
Keywords: Hepatocellular Carcinoma, Copper, cuproptosis, cuproptosis-related genes, copper chelators, copper ionophores
Received: 05 Jan 2025; Accepted: 09 Jul 2025.
Copyright: © 2025 Liang, Wang, Wu, Huang, Zhang and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Feng Jiang, 广西中医药大学附属瑞康医院, 南宁市, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.