Investigation of Lipid Metabolism Reveals Novel Vulnerabilities to Ferroptosis in Glioblastoma
Abstract
Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Despite standard of care, which includes tumor resection, chemotherapy, and radiation, patient prognosis remains poor, with a median survival of 11-15 months. However, for Veterans, both median survival and survival rate are lower, indicating an unmet need for effective therapeutic strategies for the treatment of this disease for both the Veteran community and the general population. The key barrier to successful therapeutic design is our lack of understanding of the mechanisms that drive GBM tumor growth. Therefore, it is essential that GBM tumor cell biology is further investigated to identify unique tumor-specific vulnerabilities for the development of novel and effective therapies. Many cancers, including GBM, frequently alter their lipid metabolism in order to meet the demands of the rapidly dividing cancer cells. While it has been shown that lipid composition is different in GBM tumors compared to the surrounding normal brain, it is not fully understood how this occurs, or why. We aim to investigate the mechanism by which lipid metabolism is altered in GBM and determine if that metabolic rewiring provides us with a therapeutic opportunity. We investigated GBM samples to study their lipid composition and genetics and were able to identify a molecularly defined subset of samples with a specific lipid composition. Interestingly, this subset of patient samples was also more susceptible to cell death in vitro via a novel mechanism called ferroptosis. With this research project, we aim to determine the mechanism by which lipids are altered in this subset of GBM samples and to understand how that change in lipid composition can sensitize cells to ferroptosis. Completion of this work will advance the field of cancer biology and shed light on specific novel mechanisms of metabolic reprograming. Most importantly, we aim to translate our findings into a novel therapy for the treatment of GBM in patients. This research award will enable Ms. Morrow to complete her proposed research project and continue this line of research into the future of her scientific career. Ms. Morrow will be involved in a research development plan that involves productive, interdisciplinary collaborations with experts that will both guide and train her throughout her proposed research.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010453
Entities
People
- Danielle Morrow
Organizations
- United States Army
- University of California, Los Angeles