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Cells
Volume 15
Issue 12
10.3390/cells15121087
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Review

Metabolic and Post-Translational Vulnerabilities of Glioblastoma: Disulfidptosis, Glycosylation, and Implications for CAR-T Therapy

by
Tadeusz Strózik
1,2,*,
Adrianna Rutkowska
1,2,
Tomasz Wasiak
1,2,
Damian Ciunowicz
1,2,
Piotr Rieske
2,3,
Natalia Szczepaniak
1,4 and
Ewelina Stoczyńska-Fidelus
1,2
1
Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7/9 St., 90-752 Lodz, Poland
2
Department of Research and Development, LEK-AM Pharmaceutical Company Ltd., Inwestycyjna 7 St., 95-050 Konstantynow Lodzki, Poland
3
Department of Tumor Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7/9 St., 90-752 Lodz, Poland
4
Student Scientific Circle at the Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7/9 St., 90-752 Lodz, Poland
*
Author to whom correspondence should be addressed.
Cells 2026, 15(12), 1087; https://doi.org/10.3390/cells15121087 (registering DOI)
Submission received: 30 April 2026 / Revised: 4 June 2026 / Accepted: 12 June 2026 / Published: 15 June 2026
(This article belongs to the Special Issue Cell Death Mechanisms and Therapeutic Opportunities in Glioblastoma)
Versions Notes

Abstract

Glioblastoma (GB) remains one of the most therapy-resistant solid tumors, characterized by profound metabolic plasticity, intratumoral heterogeneity, and a highly immunosuppressive microenvironment. While immunotherapies such as chimeric antigen receptor T (CAR-T) cells have shown promise in hematological malignancies, their efficacy in GB has been limited. Emerging evidence suggests that tumor-specific metabolic dependencies and post-translational modifications (PTMs) may represent exploitable vulnerabilities. This review discusses disulfidptosis, a recently described form of regulated cell death driven by disulfide stress under conditions of limited reducing capacity, as a context-dependent metabolic–redox vulnerability in GB. We further discuss how altered protein glycosylation and glycocalyx architecture in glioblastoma regulate cell survival, death signaling, and immune recognition. Particular emphasis is placed on the glycosylation of surface antigens targeted by CAR-T cells, including EGFR/EGFRvIII, IL-13Rα2, mesothelin, B7-H3, HER2, and GD2, and on how glycan-dependent epitope accessibility may limit therapeutic efficacy. Finally, we distinguish disulfidptosis, whose direct relevance to CAR-T-cell responses remains to be established, from glycosylation and glycocalyx remodeling as more direct determinants of target–antigen accessibility and immune recognition. Therapeutic strategies addressing these vulnerabilities may provide rational opportunities to improve CAR-T-based and combinatorial therapies for GB.
Keywords: glioblastoma; disulfidptosis; SLC7A11/xCT; redox homeostasis; metabolic plasticity; glycosylation; glycocalyx; antigen accessibility; antigen shedding; CAR-T cell therapy glioblastoma; disulfidptosis; SLC7A11/xCT; redox homeostasis; metabolic plasticity; glycosylation; glycocalyx; antigen accessibility; antigen shedding; CAR-T cell therapy

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MDPI and ACS Style

Strózik, T.; Rutkowska, A.; Wasiak, T.; Ciunowicz, D.; Rieske, P.; Szczepaniak, N.; Stoczyńska-Fidelus, E. Metabolic and Post-Translational Vulnerabilities of Glioblastoma: Disulfidptosis, Glycosylation, and Implications for CAR-T Therapy. Cells 2026, 15, 1087. https://doi.org/10.3390/cells15121087

AMA Style

Strózik T, Rutkowska A, Wasiak T, Ciunowicz D, Rieske P, Szczepaniak N, Stoczyńska-Fidelus E. Metabolic and Post-Translational Vulnerabilities of Glioblastoma: Disulfidptosis, Glycosylation, and Implications for CAR-T Therapy. Cells. 2026; 15(12):1087. https://doi.org/10.3390/cells15121087

Chicago/Turabian Style

Strózik, Tadeusz, Adrianna Rutkowska, Tomasz Wasiak, Damian Ciunowicz, Piotr Rieske, Natalia Szczepaniak, and Ewelina Stoczyńska-Fidelus. 2026. "Metabolic and Post-Translational Vulnerabilities of Glioblastoma: Disulfidptosis, Glycosylation, and Implications for CAR-T Therapy" Cells 15, no. 12: 1087. https://doi.org/10.3390/cells15121087

APA Style

Strózik, T., Rutkowska, A., Wasiak, T., Ciunowicz, D., Rieske, P., Szczepaniak, N., & Stoczyńska-Fidelus, E. (2026). Metabolic and Post-Translational Vulnerabilities of Glioblastoma: Disulfidptosis, Glycosylation, and Implications for CAR-T Therapy. Cells, 15(12), 1087. https://doi.org/10.3390/cells15121087

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