Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

Disulfidptosis in cancer: from redox stress to therapeutic strategy

Cancer Gene Therapy volume 33, pages 22–25 (2026)Cite this article

Subjects

Abstract

Disulfidptosis, a recently identified form of disulfide-dependent cell death, has emerged as a key regulator of cancer progression and therapy resistance. This review examines the molecular mechanisms connecting the redox balance within the tumor microenvironment (TME), outlines its crosstalk with traditional cell death pathways, and highlights its promise as a therapeutic strategy. Current evidence indicates that disulfidptosis is driven by glutathione (GSH) depletion and thiol-disulfide exchange imbalance, leading to endoplasmic reticulum stress and tumor cell vulnerability. Translational applications—including small-molecule activators and combination therapies—are discussed, alongside challenges in clinical translation and future research directions.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Molecular mechanisms underlying tumor cell disulfidptosis and potential clinical targeting strategies.

Similar content being viewed by others

References

  1. Zhang R, Kang R, Tang D. Reductive cell death: the other side of the coin. Cancer Gene Ther. 2023;30:929–31.

    Article  CAS  PubMed  Google Scholar 

  2. Liu X, Nie L, Zhang Y, Yan Y, Wang C, Colic M, et al. Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. Nat Cell Biol. 2023;25:404–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Liu X, Zhuang L, Gan B. Disulfidptosis: disulfide stress-induced cell death. Trends Cell Biol. 2024;34:327–37.

    Article  CAS  PubMed  Google Scholar 

  4. Xie J, Deng X, Xie Y, Zhu H, Liu P, Deng W, et al. Multi-omics analysis of disulfidptosis regulators and therapeutic potential reveals glycogen synthase 1 as a disulfidptosis triggering target for triple-negative breast cancer. MedComm. 2024;5:e502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wan J, Shi JH, Shi M, Huang H, Zhang Z, Li W, et al. Lactate dehydrogenase B facilitates disulfidptosis and exhaustion of tumour-infiltrating CD8(+) T cells. Nat Cell Biol. 2025;27:972–82.

    Article  CAS  PubMed  Google Scholar 

  6. Shi M, Li X, Guo Y, Zhang Y, Xu J, Yan L, et al. Gaudichaudione H enhances the sensitivity of hepatocellular carcinoma cells to disulfidptosis via regulating NRF2-SLC7A11 signaling pathway. Adv Sci. 2025;12:e2411131.

    Article  Google Scholar 

  7. Wang J, Chen J, Fan K, Wang M, Gao M, Ren Y, et al. Inhibition of endoplasmic reticulum stress cooperates with SLC7A11 to promote disulfidptosis and suppress tumor growth upon glucose limitation. Adv Sci. 2025;12:e2408789.

    Article  Google Scholar 

  8. Hu H, Hua S, Lu F, Zhang W, Zhang Z, Cui J, et al. Mucous permeable nanoparticle for inducing cuproptosis-like death in broad-spectrum bacteria for nebulized treatment of acute pneumonia. Adv Sci. 2025;12:e2408580.

    Article  Google Scholar 

  9. Hwang SM, Chang S, Rodriguez PC, Cubillos-Ruiz JR. Endoplasmic reticulum stress responses in anticancer immunity. Nat Rev Cancer. 2025;25:684–702.

  10. Pagliaro L, Marchesini M, Roti G. Targeting oncogenic Notch signaling with SERCA inhibitors. J Hematol Oncol. 2021;14:8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lehmann BD, Pietenpol JA. Targeting mutant p53 in human tumors. J Clin Oncol. 2012;30:3648–50.

    Article  CAS  PubMed  Google Scholar 

  12. Liang HY, Luo RZ, Deng R, Chen SL, Liu X, Yang X, et al. Glycogen stores mediated by the p53-GYS1 feedback circuit engenders platinum resistance in ovarian clear cell carcinoma. Cell Death Differ. 2025;32:1707–21.

  13. Zhang M, Zheng H, Zhu X, Liu S, Jin H, Chen Y, et al. Synchronously evoking disulfidptosis and ferroptosis via systematical glucose deprivation targeting SLC7A11/GSH/GPX4 antioxidant axis. ACS Nano. 2025;19:14233–48.

    Article  CAS  PubMed  Google Scholar 

  14. Zhu Y, Wang X, Feng L, Zhao R, Yu C, Liu Y, et al. Intermetallics triggering pyroptosis and disulfidptosis in cancer cells promote anti-tumor immunity. Nat Commun. 2024;15:8696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zheng Z, Song Y. Integrated analysis of disulfidptosis-related genes SLC7A11, SLC3A2, RPN1 and NCKAP1 across cancers. Discov Oncol. 2024;15:724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang B, Wang W, Wang Y, Wen X, Wang Z, Leng H, et al. Analysis and experimental validation of disulfidptosis related genes solute carrier family 3 member 2 (SLC3A2) in endometrial cancer. Cancer Cell Int. 2024;24:390.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhang X, Lin Y, Shi L, Zhai A, Wu C, Zhu QY. Disulfidptosis-related gene SLC3A2: a novel prognostic biomarker in nasopharyngeal carcinoma and head and neck squamous cell carcinoma. Front Oncol. 2025;15:1451034.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zong Y, Zhu A, Liu P, Fu P, Li Y, Chen S, et al. Pan-cancer analysis of the disulfidptosis-related gene RPN1 and its potential biological function and prognostic significance in gliomas. Heliyon. 2024;10:e31875.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhou Q, Song B, He Y, Zhang Z, Chen S, Chen W, et al. Identification of a disulfidptosis-related genes signature for diagnostic and immune infiltration characteristics in cervical cancer. PLoS One. 2025;20:e0322387.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wang Y, Tsukamoto Y, Hori M, Iha H. Disulfidptosis: a novel prognostic criterion and potential treatment strategy for diffuse large B-cell lymphoma (DLBCL). Int J Mol Sci. 2024;25:7156.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Che C, Song D, Xue P, Yin X. A novel disulfidptosis-related risk signature for prognostic prediction in patients with ewing sarcoma. J Orthop Res. 2025;43:790–802.

    Article  PubMed  Google Scholar 

  22. Han L, Li Y, Yu Y, Liu G, Gao X, Wang F, et al. Integrated analysis and experiments uncover the function of disulfidptosis in predicting immunotherapy effectiveness and delineating immune landscapes in uterine corpus endometrial carcinoma. Front Immunol. 2024;15:1454730.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hu G, Yao H, Wei Z, Li L, Yu Z, Li J, et al. A bioinformatics approach to identify a disulfidptosis-related gene signature for prognostic implication in colon adenocarcinoma. Sci Rep. 2023;13:12403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Zhang X, Hong B, Li H, Sun Z, Zhao J, Li M, et al. Disulfidptosis and ferroptosis related genes define the immune microenvironment and NUBPL serves as a potential biomarker for predicting prognosis and immunotherapy response in bladder cancer. Heliyon. 2024;10:e37638.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Liu L, Zhang F, Yu J, Dong P, Deng J, Liu W, et al. Multidisciplinary analysis of the prognosis and biological function of NUBPL in gastric cancer. Front Immunol. 2025;16:1603898.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sun Y, Wang R, Li X, Zhou W, Huang H, Zhou Y, et al. The involvement of lncRNA EMSLR in the disulfidptosis and progression of endometrial carcinoma. Cancer Gene Ther. 2025;32:1107–19. https://doi.org/10.1038/s41417-025-00918-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. These authors contributed equally: Xinpei Deng, Chengyi Zhang, Jindong Xie.

Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

    Xinpei Deng, Jindong Xie, Xingliang Tan & Yutian Zou

  2. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China

    Chengyi Zhang

  3. International School, Jinan University, Guangzhou, China

    Binbin Tang

Authors
  1. Xinpei Deng
    View author publications

    Search author on:PubMed Google Scholar

  2. Chengyi Zhang
    View author publications

    Search author on:PubMed Google Scholar

  3. Jindong Xie
    View author publications

    Search author on:PubMed Google Scholar

  4. Binbin Tang
    View author publications

    Search author on:PubMed Google Scholar

  5. Xingliang Tan
    View author publications

    Search author on:PubMed Google Scholar

  6. Yutian Zou
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Writing-original draft: XD, CZ, JX, BT, XT and YZ; Writing-review & editing: XD and YZ. All authors contributed to the article and approved the submitted version.

Corresponding authors

Correspondence to Xingliang Tan or Yutian Zou.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Deng, X., Zhang, C., Xie, J. et al. Disulfidptosis in cancer: from redox stress to therapeutic strategy. Cancer Gene Ther 33, 22–25 (2026). https://doi.org/10.1038/s41417-025-00985-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41417-025-00985-7

Search

Advanced search

Quick links