Stem Cell Theory of Cancer: Clinical Implications for Cellular Metabolism and Anti-Cancer Metabolomics
Although Otto Warburg may be right about the role of glycolysis versus OXPHOS in cancer metabolism, it remains unclear whether an altered metabolism is causative or correlative and is the main driver or a mere passenger in the pathogenesis of cancer. Currently, most of our successful treatments are...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/3/624 |
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| author | Shi-Ming Tu Jim Z. Chen Sunny R. Singh Sanjay Maraboyina Neriman Gokden Ping-Ching Hsu Timothy Langford |
| author_facet | Shi-Ming Tu Jim Z. Chen Sunny R. Singh Sanjay Maraboyina Neriman Gokden Ping-Ching Hsu Timothy Langford |
| author_sort | Shi-Ming Tu |
| collection | DOAJ |
| description | Although Otto Warburg may be right about the role of glycolysis versus OXPHOS in cancer metabolism, it remains unclear whether an altered metabolism is causative or correlative and is the main driver or a mere passenger in the pathogenesis of cancer. Currently, most of our successful treatments are designed to eliminate non-cancer stem cells (non-CSCs) such as differentiated cancer cells. When the treatments also happen to control CSCs or the stem-ness niche, it is often unintended, unexpected, or undetected for lack of a pertinent theory about the origin of cancer that clarifies whether cancer is a metabolic, genetic, or stem cell disease. Perhaps cellular context matters. After all, metabolic activity may be different in different cell types and their respective microenvironments—whether it is in a normal progenitor stem cell vs. progeny differentiated cell and whether it is in a malignant CSC vs. non-CSC. In this perspective, we re-examine different types of cellular metabolism, e.g., glycolytic vs. mitochondrial, of glucose, glutamine, arginine, and fatty acids in CSCs and non-CSCs. We revisit the Warburg effect, an obesity epidemic, the aspartame story, and a ketogenic diet. We propose that a pertinent scientific theory about the origin of cancer and of cancer metabolism influences the direction of cancer research as well as the design of drug versus therapy development in cancer care. |
| first_indexed | 2024-03-08T03:59:53Z |
| format | Article |
| id | doaj.art-abf54fcf5b074e7495d4e5b74a209869 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-08T03:59:53Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-abf54fcf5b074e7495d4e5b74a2098692024-02-09T15:09:23ZengMDPI AGCancers2072-66942024-01-0116362410.3390/cancers16030624Stem Cell Theory of Cancer: Clinical Implications for Cellular Metabolism and Anti-Cancer MetabolomicsShi-Ming Tu0Jim Z. Chen1Sunny R. Singh2Sanjay Maraboyina3Neriman Gokden4Ping-Ching Hsu5Timothy Langford6Division of Hematology and Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADivision of Hematology and Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADivision of Hematology and Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADepartment of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADepartment of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADepartment of Environmental & Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADepartment of Urology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USAAlthough Otto Warburg may be right about the role of glycolysis versus OXPHOS in cancer metabolism, it remains unclear whether an altered metabolism is causative or correlative and is the main driver or a mere passenger in the pathogenesis of cancer. Currently, most of our successful treatments are designed to eliminate non-cancer stem cells (non-CSCs) such as differentiated cancer cells. When the treatments also happen to control CSCs or the stem-ness niche, it is often unintended, unexpected, or undetected for lack of a pertinent theory about the origin of cancer that clarifies whether cancer is a metabolic, genetic, or stem cell disease. Perhaps cellular context matters. After all, metabolic activity may be different in different cell types and their respective microenvironments—whether it is in a normal progenitor stem cell vs. progeny differentiated cell and whether it is in a malignant CSC vs. non-CSC. In this perspective, we re-examine different types of cellular metabolism, e.g., glycolytic vs. mitochondrial, of glucose, glutamine, arginine, and fatty acids in CSCs and non-CSCs. We revisit the Warburg effect, an obesity epidemic, the aspartame story, and a ketogenic diet. We propose that a pertinent scientific theory about the origin of cancer and of cancer metabolism influences the direction of cancer research as well as the design of drug versus therapy development in cancer care.https://www.mdpi.com/2072-6694/16/3/624metabolismcancer stem cellsglycolysisOXPHOSPGC-1EMT |
| spellingShingle | Shi-Ming Tu Jim Z. Chen Sunny R. Singh Sanjay Maraboyina Neriman Gokden Ping-Ching Hsu Timothy Langford Stem Cell Theory of Cancer: Clinical Implications for Cellular Metabolism and Anti-Cancer Metabolomics Cancers metabolism cancer stem cells glycolysis OXPHOS PGC-1 EMT |
| title | Stem Cell Theory of Cancer: Clinical Implications for Cellular Metabolism and Anti-Cancer Metabolomics |
| title_full | Stem Cell Theory of Cancer: Clinical Implications for Cellular Metabolism and Anti-Cancer Metabolomics |
| title_fullStr | Stem Cell Theory of Cancer: Clinical Implications for Cellular Metabolism and Anti-Cancer Metabolomics |
| title_full_unstemmed | Stem Cell Theory of Cancer: Clinical Implications for Cellular Metabolism and Anti-Cancer Metabolomics |
| title_short | Stem Cell Theory of Cancer: Clinical Implications for Cellular Metabolism and Anti-Cancer Metabolomics |
| title_sort | stem cell theory of cancer clinical implications for cellular metabolism and anti cancer metabolomics |
| topic | metabolism cancer stem cells glycolysis OXPHOS PGC-1 EMT |
| url | https://www.mdpi.com/2072-6694/16/3/624 |
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