Targeting the Sphingolipid Rheostat in Gliomas
Gliomas are highly aggressive cancer types that are in urgent need of novel drugs and targeted therapies. Treatment protocols have not improved in over a decade, and glioma patient survival remains among the worst of all cancer types. As a result, cancer metabolism research has served as an innovati...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/16/9255 |
| _version_ | 1797444822818095104 |
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| author | Faris Zaibaq Tyrone Dowdy Mioara Larion |
| author_facet | Faris Zaibaq Tyrone Dowdy Mioara Larion |
| author_sort | Faris Zaibaq |
| collection | DOAJ |
| description | Gliomas are highly aggressive cancer types that are in urgent need of novel drugs and targeted therapies. Treatment protocols have not improved in over a decade, and glioma patient survival remains among the worst of all cancer types. As a result, cancer metabolism research has served as an innovative approach to identifying novel glioma targets and improving our understanding of brain tumors. Recent research has uncovered a unique metabolic vulnerability in the sphingolipid pathways of gliomas that possess the IDH1 mutation. Sphingolipids are a family of lipid signaling molecules that play a variety of second messenger functions in cellular regulation. The two primary metabolites, sphingosine-1-phosphate (S1P) and ceramide, maintain a rheostat balance and play opposing roles in cell survival and proliferation. Altering the rheostat such that the pro-apoptotic signaling of the ceramides outweighs the pro-survival S1P signaling in glioma cells diminishes the hallmarks of cancer and enhances tumor cell death. Throughout this review, we discuss the sphingolipid pathway and identify the enzymes that can be most effectively targeted to alter the sphingolipid rheostat and enhance apoptosis in gliomas. We discuss each pathway’s steps based on their site of occurrence in the organelles and postulate novel targets that can effectively exploit this vulnerability. |
| first_indexed | 2024-03-09T13:17:01Z |
| format | Article |
| id | doaj.art-f741ba1d5c4248c8a265b81929ca37be |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:17:01Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f741ba1d5c4248c8a265b81929ca37be2023-11-30T21:35:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316925510.3390/ijms23169255Targeting the Sphingolipid Rheostat in GliomasFaris Zaibaq0Tyrone Dowdy1Mioara Larion2Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USANeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USANeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USAGliomas are highly aggressive cancer types that are in urgent need of novel drugs and targeted therapies. Treatment protocols have not improved in over a decade, and glioma patient survival remains among the worst of all cancer types. As a result, cancer metabolism research has served as an innovative approach to identifying novel glioma targets and improving our understanding of brain tumors. Recent research has uncovered a unique metabolic vulnerability in the sphingolipid pathways of gliomas that possess the IDH1 mutation. Sphingolipids are a family of lipid signaling molecules that play a variety of second messenger functions in cellular regulation. The two primary metabolites, sphingosine-1-phosphate (S1P) and ceramide, maintain a rheostat balance and play opposing roles in cell survival and proliferation. Altering the rheostat such that the pro-apoptotic signaling of the ceramides outweighs the pro-survival S1P signaling in glioma cells diminishes the hallmarks of cancer and enhances tumor cell death. Throughout this review, we discuss the sphingolipid pathway and identify the enzymes that can be most effectively targeted to alter the sphingolipid rheostat and enhance apoptosis in gliomas. We discuss each pathway’s steps based on their site of occurrence in the organelles and postulate novel targets that can effectively exploit this vulnerability.https://www.mdpi.com/1422-0067/23/16/9255sphingolipidsceramidesphingosine-1-phosphaterheostatbrain tumorsisocitrate dehydrogenase 1 mutation |
| spellingShingle | Faris Zaibaq Tyrone Dowdy Mioara Larion Targeting the Sphingolipid Rheostat in Gliomas International Journal of Molecular Sciences sphingolipids ceramide sphingosine-1-phosphate rheostat brain tumors isocitrate dehydrogenase 1 mutation |
| title | Targeting the Sphingolipid Rheostat in Gliomas |
| title_full | Targeting the Sphingolipid Rheostat in Gliomas |
| title_fullStr | Targeting the Sphingolipid Rheostat in Gliomas |
| title_full_unstemmed | Targeting the Sphingolipid Rheostat in Gliomas |
| title_short | Targeting the Sphingolipid Rheostat in Gliomas |
| title_sort | targeting the sphingolipid rheostat in gliomas |
| topic | sphingolipids ceramide sphingosine-1-phosphate rheostat brain tumors isocitrate dehydrogenase 1 mutation |
| url | https://www.mdpi.com/1422-0067/23/16/9255 |
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