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Unlocking glioma vulnerabilities: targeting regulated cell death pathways for innovative therapies
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  • Review Article
  • Open access
  • Published: 10 February 2026

Unlocking glioma vulnerabilities: targeting regulated cell death pathways for innovative therapies

  • Jincai Guo1,
  • Lijuan Zong2,
  • Ying Huang3,
  • Xiang Liu4,
  • Yixiang Hu  ORCID: orcid.org/0000-0001-8697-644X4 &
  • …
  • Ya Liu  ORCID: orcid.org/0000-0003-4540-954X4 

Cell Death Discovery , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Cell death
  • CNS cancer

Abstract

Glioma, the most prevalent primary brain tumor, primarily arises from glial cells or their progenitors. Histologically, gliomas are classified into astrocytomas, oligodendrogliomas, and ependymomas. Due to their aggressive invasive nature and resistance to chemotherapy, gliomas exhibit high recurrence rates and poor clinical outcomes. Regulated cell death (RCD) refers to a set of genetically controlled cellular processes that significantly influence tumor behavior. RCD plays a dual role in cancer: under normal physiological conditions, it eliminates malignant cells to prevent tumorigenesis, while in pathological conditions, tumor cells evade RCD to gain survival advantages. Furthermore, distinct RCD pathways can modulate the tumor immune microenvironment, thereby affecting therapeutic outcomes. Targeting RCD mechanisms presents a promising strategy to overcome therapeutic resistance and advance innovative glioma immunotherapies. This review explores the molecular mechanisms of pyroptosis, ferroptosis, necroptosis, and autophagy in glioma, emphasizing their critical roles in tumor progression. It also examines therapeutic strategies targeting RCD, including recent advancements in glutathione peroxidase 4 (GPX4) inhibitors, oncolytic virotherapy, and other emerging agents. Furthermore, the review discusses the potential of nanoparticle-based drug delivery systems and multi-omics approaches to optimize personalized combination therapies, aiming to enhance multimodal, synergistic interventions for more effective glioma management.

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Acknowledgements

This work was supported by funding from the National Natural Science Foundation of China (No. 81473339), the Hunan Provincial Natural Science Foundation of China (No.2024JJ9532), and the Hunan Provincial Administration of Traditional Chinese Medicine Project (No. E2023026).

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Authors and Affiliations

  1. Department of Pharmacy, Changsha Stomatological Hospital, Changsha, China

    Jincai Guo

  2. Department of Rehabilitation Medicine, Zhongda Hospital of Southeast University, Nanjing, China

    Lijuan Zong

  3. Zhongshan Hospital of Traditional Chinese Medicine Afflilated to Guangzhou University of Chinese Medicine, Zhongshan, China

    Ying Huang

  4. Department of Clinical Pharmacy, The Central Hospital of Xiangtan (The affiliated hospital of Hunan University), Xiangtan, China

    Xiang Liu, Yixiang Hu & Ya Liu

Authors
  1. Jincai Guo
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  2. Lijuan Zong
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  3. Ying Huang
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  4. Xiang Liu
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  5. Yixiang Hu
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  6. Ya Liu
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Contributions

Conceptualization, Yixiang Hu; Original Draft Preparation, Jincai Guo, Ya Liu, and Lijuan Zong; Visualization, figures, and tables, Lijuan Zong, Ying Huang, Jincai Guo, and Xiang Liu; Supervision, Yixiang Hu and Ya Liu.

Corresponding authors

Correspondence to Yixiang Hu or Ya Liu.

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Guo, J., Zong, L., Huang, Y. et al. Unlocking glioma vulnerabilities: targeting regulated cell death pathways for innovative therapies. Cell Death Discov. (2026). https://doi.org/10.1038/s41420-026-02949-8

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  • Received: 18 June 2025

  • Revised: 23 December 2025

  • Accepted: 01 February 2026

  • Published: 10 February 2026

  • DOI: https://doi.org/10.1038/s41420-026-02949-8

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