Metabolic Features of Tumor Dormancy: Possible Therapeutic Strategies
Abstract
:Simple Summary
Abstract
1. Tumor Dormancy: Much More Than a Simple Cell Cycle Arrest
1.1. Cellular Dormancy as an Adaptive Strategy for Tumor Progression
1.2. Multiple Mechanisms Driving Tumor Cell Dormancy
1.2.1. Intracellular Mechanisms
1.2.2. Extracellular Mechanisms
1.3. Awaking Dormant Cancer Cells: A Leading Strategy for Tumor Success
2. The Metabolic Landscape of Cancer Cell Dormancy
2.1. Metabolic Modulations Regulating the Shift between Proliferation and Quiescence
2.2. Metabolic Rewiring of Tumor Cell Dormancy: Critical Adaptations toward All the Steps of Cancer Progression
2.2.1. Metabolic Adaptations Supporting Cellular Dormancy in Primary Tumors
2.2.2. Metabolic Adaptations Supporting Tumor Dormancy throughout the Metastatic Cascade
2.2.3. Metabolic Adaptations of Dormant CSCs
2.2.4. Metabolic Adaptations of Therapy-Induced Dormant Cells
2.3. Different Metabolic Strategies Exploiting Tumor Escape from Dormancy
3. Novel Approaches to Eradicate Dormant Cells
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Tumor Type | Metastatic Site | Dormancy Factor | Mechanism | Ref | CSC Markers | Ref |
---|---|---|---|---|---|---|
Breast | Lung | Fbxw7 | Increased levels | [34] | CD44+CD24−/low ALDH+ | [192,193] |
Lung | ATG7 | Increased levels | [63] | |||
Lung | CXCR4 | Decreased levels | [194] | |||
Lung | OXPHOS | Activation | [142,164,173] | |||
ARHI | Increased levels | [58] | ||||
IFN-β/IFNAR/IRF7 | Activation | [80] | ||||
NRF2 | Activation | [150] | ||||
Bone marrow | LIFR | Increased levels | [108] | |||
Bone | MSK1 | Increased levels | [195] | |||
Multiple sites | IKKβ | Activation | [76] | |||
Intraperitoneal | KiSS1 | Increased levels | [35] | |||
Lung | NR2F1/DEC2/p27 | Increased levels | [100] | |||
AMPK/OXPHOS | Activation | [147] | ||||
HNSCC | Lymph nodes | PRRX1 | Increased levels | [196] | CD44+ ALDH+ BMI-1 | [197,198,199] |
Bone marrow | NR2F1/NANOG | Increased levels | [41,99] | |||
Bone marrow | TGFβ2 | Increased levels | [200] | |||
Melanoma | Lung | KiSS1 | Increased levels | [37] | ABCB5+ CD20+ CD271+ | [201,202,203] |
OXPHOS | Activation | [143,144] | ||||
Ovarian | KiSS1 | Increased levels | [36] | CD44+, CD117+ CD133+ SP | [204,205,206] | |
Intraperitoneal sites | MKK4 | Increased levels | [207] | |||
ARHI | Increased levels | [56,57] | ||||
Prostate | Lipid metabolism | Activation | [156] | Sca1+, CD133+ CD44+ A2β1 hi | [208,209] | |
Bone marrow | TBK1 | Increased levels | [72] | |||
Bone | BMP-7 | Increased levels | [210] | |||
Bone | Wnt5a | Increased levels | [211] | |||
Liver, Lymph node, Bone | GAS6/AXL | Increased levels | [212] | |||
Bone | GDF10/TGFβ2/TGF-βRIII | Increased levels | [213] | |||
Bone marrow | NR2F1/NANOG | Increased levels | [41] | |||
Pancreas | Liver and Lung | KRAS/C-Myc, IGF1/AKT | Activation | [51] | CD44+, CD24+, ESA+, CD133+ | [214,215,216] |
OXPHOS | Activation | [157,165] |
Drug | Mechanism of Action | Cancer Model | Ref |
---|---|---|---|
VLX600 | Iron chelator designed to interfere with intracellular iron metabolism, leading to mitochondrial OXPHOS inhibition | Colon cancer | [153] |
VLX600 | Iron chelator designed to interfere with intracellular iron metabolism, leading to mitochondrial OXPHOS inhibition | Phase I study on patients diagnosed with advanced solid tumors | [154] |
Triacsin C | Inhibitor of lipid metabolism | Prostate cancer | [156] |
CB-839 and BPTES | Glutaminase inhibitors. Inhibit the conversion of glutamine to glutamate, thereby limiting glutamate available for anaplerosis | Breast cancer | [150] |
Dorsomorphin | AMPK inhibitor | ER+ Breast cancer | [147] |
Ranolazine | FA oxidation inhibitor | ER+ Breast cancer | [147] |
Etomoxir | FA oxidation inhibitor | ER+ Breast cancer | [147] |
Perhexiline | FA oxidation inhibitor | ER+ Breast cancer | [147] |
Oligomycin | ETC complex V inhibitor, OXPHOS inhibitor | Breast cancer metastasizing the lung | [173] |
IACS-010759 | ECT complex I inhibitor, OXPHOS inhibitor | Melanoma brain metastases | [176] |
IACS-010759 | ECT complex I inhibitor, OXPHOS inhibitor | Acute Myeloid Leukemia | NCT02882321 |
IACS-010759 | ECT complex I inhibitor, OXPHOS inhibitor | Lymphoma | NCT03291938 |
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Pranzini, E.; Raugei, G.; Taddei, M.L. Metabolic Features of Tumor Dormancy: Possible Therapeutic Strategies. Cancers 2022, 14, 547. https://doi.org/10.3390/cancers14030547
Pranzini E, Raugei G, Taddei ML. Metabolic Features of Tumor Dormancy: Possible Therapeutic Strategies. Cancers. 2022; 14(3):547. https://doi.org/10.3390/cancers14030547
Chicago/Turabian StylePranzini, Erica, Giovanni Raugei, and Maria Letizia Taddei. 2022. "Metabolic Features of Tumor Dormancy: Possible Therapeutic Strategies" Cancers 14, no. 3: 547. https://doi.org/10.3390/cancers14030547
APA StylePranzini, E., Raugei, G., & Taddei, M. L. (2022). Metabolic Features of Tumor Dormancy: Possible Therapeutic Strategies. Cancers, 14(3), 547. https://doi.org/10.3390/cancers14030547