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Regulated cell death modalities: breaking resistance of temozolomide glioblastoma therapy

Tatiana A Mishchenko1, Oluwabukolami J Olajide1, Ekaterina N Gorshkova1

  • 1Institute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia.

Trends in Cancer
|February 11, 2025
PubMed

Insights

Temozolomide chemotherapy can trigger various cell death types in glioblastoma. Harnessing these cell deaths may overcome treatment resistance and improve glioblastoma therapy outcomes.

Area of Science:

  • Oncology
  • Cancer Biology
  • Immunotherapy

Background:

  • Temozolomide (TMZ) is the standard first-line chemotherapy for glioblastoma multiforme (GBM).
  • Despite its use, GBM remains a challenging disease with significant limitations in current therapeutic strategies.
  • Understanding the mechanisms of TMZ resistance is crucial for developing more effective treatments.

Purpose of the Study:

  • To critically assess Temozolomide's potential to induce multiple regulated cell death modalities in GBM.
  • To explore the immunogenic properties of these cell death pathways.
  • To develop novel therapeutic strategies for overcoming GBM resistance and enhancing treatment efficacy.

Main Methods:

  • Investigating the induction of various regulated cell death pathways by Temozolomide.
  • Analyzing the immunogenic consequences of Temozolomide-induced cell death.
  • Developing and evaluating novel combination therapies targeting GBM.

Main Results:

  • Temozolomide can induce multiple forms of regulated cell death.
  • These cell death modalities possess immunogenic properties that can be leveraged.
  • Preliminary data suggests potential for enhanced GBM therapy.

Conclusions:

  • Temozolomide's ability to induce immunogenic cell death offers new therapeutic avenues.
  • Targeting these pathways could overcome glioblastoma resistance.
  • Further research is warranted to translate these findings into clinical practice.
Keywords:
ICDapoptosischemotherapyferroptosisglioblastomagliomaimmunogenic cell deathmixed types of cell deathnecroptosispyroptosisresistance mechanisms

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