Metabolic management of microenvironment acidity in glioblastoma
Glioblastoma (GBM), similar to most cancers, is dependent on fermentation metabolism for the synthesis of biomass and energy (ATP) regardless of the cellular or genetic heterogeneity seen within the tumor. The transition from respiration to fermentation arises from the documented defects in the numb...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.968351/full |
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| author | Thomas N. Seyfried Gabriel Arismendi-Morillo Giulio Zuccoli Derek C. Lee Tomas Duraj Ahmed M. Elsakka Joseph C. Maroon Purna Mukherjee Linh Ta Laura Shelton Dominic D'Agostino Michael Kiebish Christos Chinopoulos |
| author_facet | Thomas N. Seyfried Gabriel Arismendi-Morillo Giulio Zuccoli Derek C. Lee Tomas Duraj Ahmed M. Elsakka Joseph C. Maroon Purna Mukherjee Linh Ta Laura Shelton Dominic D'Agostino Michael Kiebish Christos Chinopoulos |
| author_sort | Thomas N. Seyfried |
| collection | DOAJ |
| description | Glioblastoma (GBM), similar to most cancers, is dependent on fermentation metabolism for the synthesis of biomass and energy (ATP) regardless of the cellular or genetic heterogeneity seen within the tumor. The transition from respiration to fermentation arises from the documented defects in the number, the structure, and the function of mitochondria and mitochondrial-associated membranes in GBM tissue. Glucose and glutamine are the major fermentable fuels that drive GBM growth. The major waste products of GBM cell fermentation (lactic acid, glutamic acid, and succinic acid) will acidify the microenvironment and are largely responsible for drug resistance, enhanced invasion, immunosuppression, and metastasis. Besides surgical debulking, therapies used for GBM management (radiation, chemotherapy, and steroids) enhance microenvironment acidification and, although often providing a time-limited disease control, will thus favor tumor recurrence and complications. The simultaneous restriction of glucose and glutamine, while elevating non-fermentable, anti-inflammatory ketone bodies, can help restore the pH balance of the microenvironment while, at the same time, providing a non-toxic therapeutic strategy for killing most of the neoplastic cells. |
| first_indexed | 2024-12-10T15:44:07Z |
| format | Article |
| id | doaj.art-74eb8cee777944af80425d23672b01c8 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T15:44:07Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-74eb8cee777944af80425d23672b01c82022-12-22T01:43:01ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-08-011210.3389/fonc.2022.968351968351Metabolic management of microenvironment acidity in glioblastomaThomas N. Seyfried0Gabriel Arismendi-Morillo1Giulio Zuccoli2Derek C. Lee3Tomas Duraj4Ahmed M. Elsakka5Joseph C. Maroon6Purna Mukherjee7Linh Ta8Laura Shelton9Dominic D'Agostino10Michael Kiebish11Christos Chinopoulos12Biology Department, Boston College, Chestnut Hill, MA, United StatesInstituto de Investigaciones Biológicas, Facultad de Medicina, Universidad del Zulia, Maracaibo, VenezuelaThe Program for the Study of Neurodevelopment in Rare Disorders (NDRD), University of Pittsburgh, Pittsburgh, PA, United StatesBiology Department, Boston College, Chestnut Hill, MA, United StatesFaculty of Medicine, Institute for Applied Molecular Medicine (IMMA), CEU San Pablo University, Madrid, SpainNeuro Metabolism, Faculty of Medicine, Alexandria University, Alexandria, EgyptDepartment of Neurosurgery, University of Pittsburgh, Medical Center, Pittsburgh, PA, United StatesBiology Department, Boston College, Chestnut Hill, MA, United StatesBiology Department, Boston College, Chestnut Hill, MA, United StatesMatterworks, Somerville, MA, United StatesDepartment of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, United StatesBERG LLC, Framingham, MA, United States0Department of Medical Biochemistry, Semmelweis University, Budapest, HungaryGlioblastoma (GBM), similar to most cancers, is dependent on fermentation metabolism for the synthesis of biomass and energy (ATP) regardless of the cellular or genetic heterogeneity seen within the tumor. The transition from respiration to fermentation arises from the documented defects in the number, the structure, and the function of mitochondria and mitochondrial-associated membranes in GBM tissue. Glucose and glutamine are the major fermentable fuels that drive GBM growth. The major waste products of GBM cell fermentation (lactic acid, glutamic acid, and succinic acid) will acidify the microenvironment and are largely responsible for drug resistance, enhanced invasion, immunosuppression, and metastasis. Besides surgical debulking, therapies used for GBM management (radiation, chemotherapy, and steroids) enhance microenvironment acidification and, although often providing a time-limited disease control, will thus favor tumor recurrence and complications. The simultaneous restriction of glucose and glutamine, while elevating non-fermentable, anti-inflammatory ketone bodies, can help restore the pH balance of the microenvironment while, at the same time, providing a non-toxic therapeutic strategy for killing most of the neoplastic cells.https://www.frontiersin.org/articles/10.3389/fonc.2022.968351/fullglutaminolysisglycolysisfermentationsuccinatelactateglutamate |
| spellingShingle | Thomas N. Seyfried Gabriel Arismendi-Morillo Giulio Zuccoli Derek C. Lee Tomas Duraj Ahmed M. Elsakka Joseph C. Maroon Purna Mukherjee Linh Ta Laura Shelton Dominic D'Agostino Michael Kiebish Christos Chinopoulos Metabolic management of microenvironment acidity in glioblastoma Frontiers in Oncology glutaminolysis glycolysis fermentation succinate lactate glutamate |
| title | Metabolic management of microenvironment acidity in glioblastoma |
| title_full | Metabolic management of microenvironment acidity in glioblastoma |
| title_fullStr | Metabolic management of microenvironment acidity in glioblastoma |
| title_full_unstemmed | Metabolic management of microenvironment acidity in glioblastoma |
| title_short | Metabolic management of microenvironment acidity in glioblastoma |
| title_sort | metabolic management of microenvironment acidity in glioblastoma |
| topic | glutaminolysis glycolysis fermentation succinate lactate glutamate |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.968351/full |
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