Beyond glucose: alternative sources of energy in glioblastoma

Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. With a designation of WHO Grade IV, it is also the most lethal primary brain tumor with a median survival of just 15 months. This is often despite aggressive treatment that includes surgical resection, radiation therap...

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Bibliographic Details
Published in:Theranostics 2021, Vol.11 (5), p.2048-2057
Main Authors: Caniglia, John L, Jalasutram, Anvesh, Asuthkar, Swapna, Sahagun, Joseph, Park, Simon, Ravindra, Aditya, Tsung, Andrew J, Guda, Maheedhara R, Velpula, Kiran K
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Cancer therapies
Dehydrogenases
Energy
Energy Metabolism
Fatty acids
Glioblastoma - metabolism
Glioblastoma - pathology
Glucose
Glucose - metabolism
Humans
Hypoxia
Kinases
Metabolism
Oxidation
Phosphorylation
Preferences
Respiration
Review
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Summary:Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. With a designation of WHO Grade IV, it is also the most lethal primary brain tumor with a median survival of just 15 months. This is often despite aggressive treatment that includes surgical resection, radiation therapy, and chemotherapy. Based on the poor outcomes and prevalence of the tumor, the demand for innovative therapies continues to represent a pressing issue for clinicians and researchers. In terms of therapies targeting metabolism, the prevalence of the Warburg effect has led to a focus on targeting glucose metabolism to halt tumor progression. While glucose is the dominant source of growth substrate in GBM, a number of unique metabolic pathways are exploited in GBM to meet the increased demand for replication and progression. In this review we aim to explore how metabolites from fatty acid oxidation, the urea cycle, the glutamate-glutamine cycle, and one-carbon metabolism are shunted toward energy producing pathways to meet the high energy demand in GBM. We will also explore how the process of autophagy provides a reservoir of nutrients to support viable tumor cells. By so doing, we aim to establish a foundation of implicated metabolic mechanisms supporting growth and tumorigenesis of GBM within the literature. With the sparse number of therapeutic interventions specifically targeting metabolic pathways in GBM, we hope that this review expands further insight into the development of novel treatment modalities.
ISSN:1838-7640
1838-7640
DOI:10.7150/thno.53506