Year: 2025
Type: conference-abstract
Abstract: Glioblastoma is the most aggressive primary malignant brain tumor with dismal survival. Despite surgical resection and adjuvant therapy, the tumor almost always recurs. Tumor recurrence is enriched in treatment-resistant mesenchymal-like glioblastoma stem cells (GSCs), which represent a major obstacle to treatment. GSCs are resistant to many chemotherapies and ionizing radiation; however, recent evidence suggests that they are particularly sensitive to death by lipid peroxidation, a phenomenon known as ferroptosis. However, we found that not all GBM GSCs are sensitive to ferroptosis. Here, we propose an innovative therapeutic strategy centered on eradicating these ferroptosis-resistant GSCs by targeting their metabolic dependencies. We leveraged patient-derived GSCs as well as an ex vivo GBM slice culture model to test a new therapeutic strategy and obtained in-depth insights into GSCs and the tumor microenvironment using single-nucleus RNAseq and spatial transcriptomics. We discovered that ferroptosis sensitivity requires secreted factors from tumor microenvironment astrocytes, and have identified the mechanisms by which tumor-associated astrocytes can reverse ferroptosis resistance. This multi-faceted approach offers a promising and novel avenue for combating GBM recurrence and holds potential for treating other refractory tumors.
Source: Neuro-Oncology
Institution: Columbia University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416139893
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