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Updated: Dec 3, 2025
The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma
Published on: April 16, 2019
Temozolomide Treatment Increases Fatty Acid Uptake in Glioblastoma Stem Cells
Seamus Caragher1, Jason Miska1, Jack Shireman1
1Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, 303 E Superior Street, Chicago, IL 60611, USA.
Abstract:
Among all cancers, glioblastoma (GBM) remains one of the least treatable. One key factor in this resistance is a subpopulation of tumor cells termed glioma stem cells (GSCs). These cells are highly resistant to current treatment modalities, possess marked self-renewal capacity, and are considered key drivers of tumor recurrence. Further complicating an understanding of GBM, evidence shows that the GSC population is not a pre-ordained and static group of cells but also includes previously differentiated GBM cells that have attained a GSC state secondary to environmental cues. The metabolic behavior of GBM cells undergoing plasticity remains incompletely understood. To that end, we probed the connection between GSCs, environmental cues, and metabolism. Using patient-derived xenograft cells, mouse models, transcriptomics, and metabolic analyses, we found that cell state changes are accompanied by sharp changes in metabolic phenotype. Further, treatment with temozolomide, the current standard of care drug for GBM, altered the metabolism of GBM cells and increased fatty acid uptake both in vitro and in vivo in the plasticity driven GSC population. These results indicate that temozolomide-induced changes in cell state are accompanied by metabolic shifts-a potentially novel target for enhancing the effectiveness of current treatment modalities.
Insights
Glioblastoma stem cells (GSCs) drive tumor recurrence. This study reveals that cancer cell plasticity and temozolomide treatment induce significant metabolic shifts, offering potential new therapeutic targets.
Area of Science:
- Oncology
- Cancer Biology
- Metabolic Research
Background:
- Glioblastoma (GBM) is a highly lethal brain cancer, with glioma stem cells (GSCs) driving treatment resistance and recurrence.
- GSCs are plastic, meaning differentiated cells can revert to a stem-like state, complicating treatment strategies.
- The metabolic adaptations of GBM cells during this plasticity are not well understood.
Purpose of the Study:
- To investigate the relationship between GSC state, environmental influences, and cellular metabolism in glioblastoma.
- To understand how standard GBM treatments affect the metabolism of plastic GSC populations.
Main Methods:
- Utilized patient-derived xenograft models and in vitro cell cultures.
- Employed transcriptomics and comprehensive metabolic analyses.
- Investigated the effects of temozolomide treatment on GBM cell metabolism.
Main Results:
- Observed significant alterations in metabolic phenotype correlating with changes in GSC cell state.
- Temozolomide treatment induced metabolic changes in GBM cells, notably increasing fatty acid uptake.
- These metabolic shifts were evident in both in vitro and in vivo models, particularly in plasticity-driven GSCs.
Conclusions:
- Glioblastoma cell state plasticity is intrinsically linked to distinct metabolic profiles.
- Temozolomide, the standard GBM therapy, induces metabolic reprogramming in GSCs.
- Targeting these temozolomide-induced metabolic shifts presents a promising avenue for improving glioblastoma treatment efficacy.
