Copper is an essential trace element involved in mitochondrial metabolism, redox regulation, and enzymatic activity, and its homeostasis is critical for cell survival (Li et al., 2022). Cuproptosis is a newly defined form of regulated cell death (RCD) based on copper ion overload, whose mechanism differs from other RCDs such as apoptosis, necroptosis, pyroptosis, and ferroptosis (Tsvetkov et al., 2022). Copper mediates cuproptosis by directly binding to acyl-transferase enzymes in the tricarboxylic acid cycle, triggering protein aggregation and destabilizing iron-sulfur clusters. Extensive research has demonstrated that cuproptosis is closely linked to tumor metabolism and progression, positioning this pathway as a potential target for cancer mechanism studies and therapeutic interventions (Zhou et al., 2025).
Against this backdrop, the Research Topic was conceived to delve into the emerging biological mechanisms of cuproptosis in cancer and advance its clinical applications. Building upon the findings of Volume I, this volume compiles multiple original research papers that delve into the expression patterns of cuproptosis-related genes (CRGs) and molecules across various cancer types, including oral squamous cell carcinoma (OSCC), colorectal cancer (CRC), colorectal adenocarcinoma (COAD), cervical cancer, and rectal adenocarcinoma. Particular emphasis is placed on analyzing their critical roles in early diagnosis, prognostic evaluation, and therapeutic strategies.
Cuproptosis, as a newly discovered mechanism of RCD, has drawn widespread attention to the molecular mechanisms of its associated genes in various cancers. Liu et al. integrated multiple techniques including single-cell transcriptomics, spatial transcriptomics, and immunohistochemistry, to identify a malignant cell subtype in OSCC exhibiting metal-dependent cell death resistance (MCDR) (Liu et al.). This subtype is strongly associated with lymph node metastasis and treatment resistance, providing a potential biological biomarker for early prediction of lymph node metastasis and precision therapy. Zhuang et al. integrated multi-center clinical data, bioinformatics analysis, and in vitro/in vivo functional experiments to reveal that the CRG-ACAD8 is significantly downregulated in metastatic CRC and suppresses tumor metastasis. It exerts its anticancer effects by regulating copper ion-related pathways, immune infiltration, and chemotherapy sensitivity, providing a potential molecular target for the diagnosis, prognostic assessment, and precision treatment of colorectal cancer metastasis (Zhuang et al.). Ye et al. constructed a prognostic risk model based on multiple CRGs (ORC1, PTTG1, DLAT, PDHB), revealing the central role of cuproptosis in metabolic reprogramming, immune microenvironment modulation, and immunotherapy response, and further confirmed the therapeutic potential of inducing cuproptosis through the FDX1-elesclomol axis in COAD (Ye et al.). In cervical cancer, Cui et al. demonstrated that cuproptosis also plays an important biological role. By establishing a cuproptosis-related molecular classification and functionally validating FOXJ1, they confirmed that FOXJ1 could promote cuproptosis while suppressing tumor cell invasion, migration, and epithelial-mesenchymal transition (Cui et al.). Addressing the long-standing lack of systematic cuproptosis research in rectal adenocarcinoma, Li et al. integrated multi-omics data to establish a cuproptosis-related prognostic model, revealing the involvement of cuproptosis in tumor immune regulation and drug sensitivity (Li et al.). Across different tumor entities, researchers have explored how CRGs correlate with patient survival, tumor microenvironment composition, and immune cell infiltration, offering new insights into the interplay between metabolic cell death pathways and antitumor immunity. Some studies have further developed predictive models and risk scoring systems based on cuproptosis-related signatures, offering innovative tools for patient stratification and treatment decision-making.
Despite this, the role and mechanisms of cuproptosis in various tumor types remain to be further explored. By synthesizing these studies, this Research Topic aims to advance the in-depth investigation of cuproptosis’s role in tumor biological mechanisms and to facilitate the translation of its mechanisms into tumor precise therapeutic strategies. This Research Topic and existing evidence have indicated that cuproptosis holds significant potential for cancer metastasis diagnosis and treatment. CRGs not only serve as a potential biomarker for early diagnosis and prognostic assessment of cancer metastasis, but cuproptosis-based nanomedicines have also been developed for precision synergistic anti-metastatic therapy (Li et al., 2025). The core objective of this Research Topic is to deepen our understanding of the mechanisms linking cuproptosis and tumor, thereby paving the way for novel approaches to tumor diagnosis, prognosis assessment, and treatment through the exploitation of cuproptosis-related mechanisms.
Statements
Author contributions
BL: Writing – original draft, Writing – review and editing. CW: Writing – review and editing. JL: Writing – review and editing. CX: Writing – review and editing. L-LB: Writing – original draft, Writing – review and editing.
Funding
The author(s) declared that financial support was received for this work and/or its publication. This study was supported by Medical Young Talents Program of Hubei Province to Lin-Lin Bu.
Acknowledgments
We thank all contributing authors and reviewers for their work and dedication to this Research Topic.
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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The author(s) declared that generative AI was not used in the creation of this manuscript.
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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.
References
1
Li S.-R. Bu L.-L. Cai L. (2022). Cuproptosis: lipoylated TCA cycle proteins-mediated novel cell death pathway. Signal Transduct. Target. Ther. 2022/05/137, 158. 10.1038/s41392-022-01014-x
2
Li Z.-Z. Liu Y. Zhou K. Cao L.-M. Wang G.-R. Wu J. et al (2025). ORL@Cu-MOF boost cuproptosis and suppress fatty acid metabolism for cancer lymph node metastasis synergistic therapy. Adv. Sci.12, e02154. 10.1002/advs.202502154
3
Tsvetkov P. Coy S. Petrova B. Dreishpoon M. Verma A. Abdusamad M. et al (2022). Copper induces cell death by targeting lipoylated TCA cycle proteins. Science375, 1254–1261. 10.1126/science.abf0529
4
Zhou K. Li Z.-Z. Liu Y. Cao L.-M. Luo H.-Y. Wang G.-R. et al (2025). Cuproptosis-based nanomedicine in cancer metastasis synergistic therapy. Acta Pharm. Sin. B. 10.1016/j.apsb.2025.11.003
Summary
Keywords
cancer metastasis, cuproptosis, diagnosis, nanomedicine, regulated cell death
Citation
Liu B, Wang C, Liu J, Xu C and Bu L-L (2026) Editorial: Cuproptosis and tumors, volume II: from basic research to clinical translation. Front. Cell Dev. Biol. 13:1773248. doi: 10.3389/fcell.2025.1773248
Received
22 December 2025
Accepted
30 December 2025
Published
13 January 2026
Volume
13 - 2025
Edited and reviewed by
Shyamala Maheswaran, Harvard Medical School, United States
Updates
Copyright
© 2026 Liu, Wang, Liu, Xu and Bu.
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) and the copyright owner(s) 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: Bing Liu, liubing9909@whu.edu.cn; Jiannan Liu, laurence_ljn@163.com; Cheng Wang, wangch75@mail.sysu.edu.cn; Chun Xu, chun.xu@sydney.edu.au; Lin-Lin Bu, lin-lin.bu@whu.edu.cn
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.