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

Tadeusz Strózik1,2, Adrianna Rutkowska1,2, Tomasz Wasiak1,2

  • 1Department of Molecular Biology, Chair of Medical Biology, Medical University of Lodz, Zeligowskiego 7/9 St., 90-752 Lodz, Poland.

Cells
|June 25, 2026
PubMed

Insights

Glioblastoma (GB) is therapy-resistant due to metabolic plasticity and immune suppression. Targeting metabolic vulnerabilities like disulfidptosis and altered glycosylation may improve chimeric antigen receptor T (CAR-T) cell therapy for GB.

Area of Science:

  • Neuro-oncology
  • Cancer immunology
  • Metabolic regulation of cell death

Background:

  • Glioblastoma (GB) exhibits significant metabolic plasticity, intratumoral heterogeneity, and an immunosuppressive microenvironment, limiting treatment efficacy.
  • Chimeric antigen receptor T (CAR-T) cell therapy shows promise in hematological cancers but faces challenges in treating GB.
  • Tumor-specific metabolic dependencies and post-translational modifications (PTMs) are emerging as potential therapeutic targets in GB.

Purpose of the Study:

  • To review disulfidptosis as a metabolic-redox vulnerability in glioblastoma.
  • To discuss the role of altered protein glycosylation and glycocalyx architecture in GB cell survival, death signaling, and immune recognition.
  • To analyze how glycosylation of CAR-T cell targets impacts therapeutic efficacy.

Main Methods:

  • Literature review focusing on metabolic vulnerabilities, disulfidptosis, and protein glycosylation in glioblastoma.
  • Analysis of how altered glycosylation affects target antigen accessibility for CAR-T cells.
  • Distinguishing disulfidptosis from glycosylation/glycocalyx remodeling in the context of CAR-T therapy.

Main Results:

  • Disulfidptosis represents a context-dependent metabolic-redox vulnerability in glioblastoma.
  • Altered protein glycosylation and glycocalyx remodeling influence glioblastoma cell survival, death signaling, and immune evasion.
  • Glycan-dependent epitope accessibility on target antigens (e.g., EGFR, IL-13Rα2, B7-H3) can limit CAR-T cell efficacy.

Conclusions:

  • Disulfidptosis, while relevant to GB metabolism, requires further study for its direct role in CAR-T responses.
  • Glycosylation and glycocalyx remodeling are critical determinants of target antigen accessibility and immune recognition in glioblastoma.
  • Targeting these metabolic and glycosylation-related vulnerabilities offers potential for improved CAR-T and combination therapies for glioblastoma.
Keywords:
CAR-T cell therapySLC7A11/xCTantigen accessibilityantigen sheddingdisulfidptosisglioblastomaglycocalyxglycosylationmetabolic plasticityredox homeostasis

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