Targeting chemoresistance and mitochondria-dependent metabolic reprogramming in acute myeloid leukemia
Chemoresistance often complicates the management of cancer, as noted in the instance of acute myeloid leukemia (AML). Mitochondrial function is considered important for the viability of AML blasts and appears to also modulate chemoresistance. As mitochondrial metabolism is aberrant in AML, any disti...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1244280/full |
| _version_ | 1797690390365601792 |
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| author | Lili Feng Lili Feng Philip Y. Zhang Wenda Gao Jinming Yu Simon C. Robson Simon C. Robson |
| author_facet | Lili Feng Lili Feng Philip Y. Zhang Wenda Gao Jinming Yu Simon C. Robson Simon C. Robson |
| author_sort | Lili Feng |
| collection | DOAJ |
| description | Chemoresistance often complicates the management of cancer, as noted in the instance of acute myeloid leukemia (AML). Mitochondrial function is considered important for the viability of AML blasts and appears to also modulate chemoresistance. As mitochondrial metabolism is aberrant in AML, any distinct pathways could be directly targeted to impact both cell viability and chemoresistance. Therefore, identifying and targeting those precise rogue elements of mitochondrial metabolism could be a valid therapeutic strategy in leukemia. Here, we review the evidence for abnormalities in mitochondria metabolic processes in AML cells, that likely impact chemoresistance. We further address several therapeutic approaches targeting isocitrate dehydrogenase 2 (IDH2), CD39, nicotinamide phosphoribosyl transferase (NAMPT), electron transport chain (ETC) complex in AML and also consider the roles of mesenchymal stromal cells. We propose the term “mitotherapy” to collectively refer to such regimens that attempt to override mitochondria-mediated metabolic reprogramming, as used by cancer cells. Mounting evidence suggests that mitotherapy could provide a complementary strategy to overcome chemoresistance in liquid cancers, as well as in solid tumors. |
| first_indexed | 2024-03-12T01:59:53Z |
| format | Article |
| id | doaj.art-0f1b239aecf747c0a36e87eb31569661 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-12T01:59:53Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-0f1b239aecf747c0a36e87eb315696612023-09-07T19:17:15ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-09-011310.3389/fonc.2023.12442801244280Targeting chemoresistance and mitochondria-dependent metabolic reprogramming in acute myeloid leukemiaLili Feng0Lili Feng1Philip Y. Zhang2Wenda Gao3Jinming Yu4Simon C. Robson5Simon C. Robson6Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaCenter for Inflammation Research, Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United StatesCenter for Inflammation Research, Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United StatesAntagen Institute for Biomedical Research, Canton, MA, United StatesDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaCenter for Inflammation Research, Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United StatesDepartment of Medicine, Division of Gastroenterology/Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United StatesChemoresistance often complicates the management of cancer, as noted in the instance of acute myeloid leukemia (AML). Mitochondrial function is considered important for the viability of AML blasts and appears to also modulate chemoresistance. As mitochondrial metabolism is aberrant in AML, any distinct pathways could be directly targeted to impact both cell viability and chemoresistance. Therefore, identifying and targeting those precise rogue elements of mitochondrial metabolism could be a valid therapeutic strategy in leukemia. Here, we review the evidence for abnormalities in mitochondria metabolic processes in AML cells, that likely impact chemoresistance. We further address several therapeutic approaches targeting isocitrate dehydrogenase 2 (IDH2), CD39, nicotinamide phosphoribosyl transferase (NAMPT), electron transport chain (ETC) complex in AML and also consider the roles of mesenchymal stromal cells. We propose the term “mitotherapy” to collectively refer to such regimens that attempt to override mitochondria-mediated metabolic reprogramming, as used by cancer cells. Mounting evidence suggests that mitotherapy could provide a complementary strategy to overcome chemoresistance in liquid cancers, as well as in solid tumors.https://www.frontiersin.org/articles/10.3389/fonc.2023.1244280/fullacute myeloid leukemiachemoresistancemitochondrial metabolismmitotherapymetabolic reprogramming |
| spellingShingle | Lili Feng Lili Feng Philip Y. Zhang Wenda Gao Jinming Yu Simon C. Robson Simon C. Robson Targeting chemoresistance and mitochondria-dependent metabolic reprogramming in acute myeloid leukemia Frontiers in Oncology acute myeloid leukemia chemoresistance mitochondrial metabolism mitotherapy metabolic reprogramming |
| title | Targeting chemoresistance and mitochondria-dependent metabolic reprogramming in acute myeloid leukemia |
| title_full | Targeting chemoresistance and mitochondria-dependent metabolic reprogramming in acute myeloid leukemia |
| title_fullStr | Targeting chemoresistance and mitochondria-dependent metabolic reprogramming in acute myeloid leukemia |
| title_full_unstemmed | Targeting chemoresistance and mitochondria-dependent metabolic reprogramming in acute myeloid leukemia |
| title_short | Targeting chemoresistance and mitochondria-dependent metabolic reprogramming in acute myeloid leukemia |
| title_sort | targeting chemoresistance and mitochondria dependent metabolic reprogramming in acute myeloid leukemia |
| topic | acute myeloid leukemia chemoresistance mitochondrial metabolism mitotherapy metabolic reprogramming |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1244280/full |
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