Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins
Ovarian cancer metastization is accompanied by the development of malignant ascites, which are associated with poor prognosis. The acellular fraction of this ascitic fluid contains tumor-promoting soluble factors, bioactive lipids, cytokines, and extracellular vesicles, all of which communicate with...
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MDPI AG
2023-12-01
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Series: | International Journal of Molecular Sciences |
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Online Access: | https://www.mdpi.com/1422-0067/25/1/323 |
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author | Diana Luísa Almeida-Nunes Ricardo Silvestre Ricardo Jorge Dinis-Oliveira Sara Ricardo |
author_facet | Diana Luísa Almeida-Nunes Ricardo Silvestre Ricardo Jorge Dinis-Oliveira Sara Ricardo |
author_sort | Diana Luísa Almeida-Nunes |
collection | DOAJ |
description | Ovarian cancer metastization is accompanied by the development of malignant ascites, which are associated with poor prognosis. The acellular fraction of this ascitic fluid contains tumor-promoting soluble factors, bioactive lipids, cytokines, and extracellular vesicles, all of which communicate with the tumor cells within this peritoneal fluid. Metabolomic profiling of ovarian cancer ascites has revealed significant differences in the pathways of fatty acids, cholesterol, glucose, and insulin. The proteins involved in these pathways promote tumor growth, resistance to chemotherapy, and immune evasion. Unveiling the key role of this liquid tumor microenvironment is crucial for discovering more efficient treatment options. This review focuses on the cholesterol and insulin pathways in ovarian cancer, identifying statins and metformin as viable treatment options when combined with standard chemotherapy. These findings are supported by clinical trials showing improved overall survival with these combinations. Additionally, statins and metformin are associated with the reversal of T-cell exhaustion, positioning these drugs as potential combinatory strategies to improve immunotherapy outcomes in ovarian cancer patients. |
first_indexed | 2024-03-08T15:05:35Z |
format | Article |
id | doaj.art-abaac8c2127d4b12bc16cc06f02d9365 |
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issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-08T15:05:35Z |
publishDate | 2023-12-01 |
publisher | MDPI AG |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-abaac8c2127d4b12bc16cc06f02d93652024-01-10T14:59:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0125132310.3390/ijms25010323Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and StatinsDiana Luísa Almeida-Nunes0Ricardo Silvestre1Ricardo Jorge Dinis-Oliveira2Sara Ricardo3Differentiation and Cancer Group, Institute for Research and Innovation in Health (i3S) of the University of Porto, 4200-135 Porto, PortugalLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal1H-TOXRUN—One Health Toxicology Research Unit, University Institute of Health Sciences, CESPU, CRL, 4585-116 Gandra, PortugalDifferentiation and Cancer Group, Institute for Research and Innovation in Health (i3S) of the University of Porto, 4200-135 Porto, PortugalOvarian cancer metastization is accompanied by the development of malignant ascites, which are associated with poor prognosis. The acellular fraction of this ascitic fluid contains tumor-promoting soluble factors, bioactive lipids, cytokines, and extracellular vesicles, all of which communicate with the tumor cells within this peritoneal fluid. Metabolomic profiling of ovarian cancer ascites has revealed significant differences in the pathways of fatty acids, cholesterol, glucose, and insulin. The proteins involved in these pathways promote tumor growth, resistance to chemotherapy, and immune evasion. Unveiling the key role of this liquid tumor microenvironment is crucial for discovering more efficient treatment options. This review focuses on the cholesterol and insulin pathways in ovarian cancer, identifying statins and metformin as viable treatment options when combined with standard chemotherapy. These findings are supported by clinical trials showing improved overall survival with these combinations. Additionally, statins and metformin are associated with the reversal of T-cell exhaustion, positioning these drugs as potential combinatory strategies to improve immunotherapy outcomes in ovarian cancer patients.https://www.mdpi.com/1422-0067/25/1/323ovarian cancer metabolomicsT-cell exhaustiondrug repurposingclinical trials |
spellingShingle | Diana Luísa Almeida-Nunes Ricardo Silvestre Ricardo Jorge Dinis-Oliveira Sara Ricardo Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins International Journal of Molecular Sciences ovarian cancer metabolomics T-cell exhaustion drug repurposing clinical trials |
title | Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins |
title_full | Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins |
title_fullStr | Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins |
title_full_unstemmed | Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins |
title_short | Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins |
title_sort | enhancing immunotherapy in ovarian cancer the emerging role of metformin and statins |
topic | ovarian cancer metabolomics T-cell exhaustion drug repurposing clinical trials |
url | https://www.mdpi.com/1422-0067/25/1/323 |
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