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The ketogenic diet for the treatment of malignant glioma
Eric C Woolf1, Adrienne C Scheck1
1Neuro-Oncology Research, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013.
Abstract:
Advances in our understanding of glioma biology has led to an increase in targeted therapies in preclinical and clinical trials; however, cellular heterogeneity often precludes the targeted molecules from being found on all glioma cells, thus reducing the efficacy of these treatments. In contrast, one trait shared by virtually all tumor cells is altered (dysregulated) metabolism. Tumor cells have an increased reliance on glucose, suggesting that treatments affecting cellular metabolism may be an effective method to improve current therapies. Indeed, metabolism has been a focus of cancer research in the last few years, as many pathways long associated with tumor growth have been found to intersect metabolic pathways in the cell. The ketogenic diet (high fat, low carbohydrate and protein), caloric restriction, and fasting all cause a metabolic change, specifically, a reduction in blood glucose and an increase in blood ketones. We, and others, have demonstrated that these metabolic changes improve survival in animal models of malignant gliomas and can potentiate the anti-tumor effect of chemotherapies and radiation treatment. In this review we discuss the use of metabolic alteration for the treatment of malignant brain tumors.
Insights
Altering cellular metabolism through methods like ketogenic diets shows promise for treating malignant gliomas. These metabolic changes can improve survival and enhance the effectiveness of standard cancer treatments.
Area of Science:
- Neuro-oncology
- Metabolic pathways in cancer
- Cancer therapy
Background:
- Targeted therapies for glioma face challenges due to cellular heterogeneity.
- Altered cellular metabolism, particularly increased glucose reliance, is a hallmark of tumor cells.
- Metabolic pathways are increasingly recognized as intersecting with tumor growth pathways.
Purpose of the Study:
- To review the potential of metabolic alterations for treating malignant brain tumors.
- To discuss how interventions like ketogenic diets, caloric restriction, and fasting impact tumor metabolism.
- To highlight the synergistic effects of metabolic changes with conventional therapies.
Main Methods:
- Review of preclinical and clinical studies on metabolic interventions for malignant gliomas.
- Discussion of the physiological effects of ketogenic diets, caloric restriction, and fasting (reduced glucose, increased ketones).
- Analysis of research demonstrating improved survival in animal models of glioma.
Main Results:
- Metabolic alterations, including ketogenic diets, reduce blood glucose and increase blood ketones.
- These metabolic changes have shown improved survival in animal models of malignant gliomas.
- Metabolic interventions can potentiate the anti-tumor effects of chemotherapy and radiation.
Conclusions:
- Metabolic alteration represents a promising strategy for enhancing malignant glioma treatment.
- Dysregulated tumor cell metabolism offers a shared vulnerability across glioma subtypes.
- Combining metabolic therapies with conventional treatments may overcome treatment resistance and improve outcomes.
