Reprogramming temozolomide response in glioblastoma through regulated and immunogenic cell death modalities

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Temozolomide (TMZ) resistance is a major challenge in glioblastoma (GBM) treatment.
• Immunogenic cell death (ICD) modalities like necroptosis, ferroptosis, and pyroptosis show promise in overcoming this resistance.
• Current strategies focus on apoptosis, but a mixed cell death approach may improve outcomes.

Purpose of the Study:

• To critically evaluate TMZ's capacity to induce various regulated cell death (RCD) pathways.
• To map the crosstalk between RCD pathways and assess their ICD characteristics.
• To discuss challenges and propose novel strategies for GBM therapy.

Main Methods:

• Literature review of TMZ's effects on RCD.
• Analysis of crosstalk between apoptosis, necroptosis, ferroptosis, pyroptosis, and cuproptosis.
• Evaluation of ICD features of these pathways.

Main Results:

• TMZ can induce multiple RCD modalities beyond apoptosis.
• Complex crosstalk exists between different RCD pathways, influencing immunogenicity.
• Balancing ICD activation is crucial to prevent pro-tumorigenic effects.

Conclusions:

• A mixed cell death strategy involving multiple ICD modalities offers a promising avenue for enhancing GBM sensitivity to TMZ.
• Understanding RCD pathway crosstalk is key to developing effective GBM therapies.
• Further research is needed to optimize therapeutic strategies and improve long-term patient outcomes.