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...

Full description

Bibliographic Details
Main Authors: Diana Luísa Almeida-Nunes, Ricardo Silvestre, Ricardo Jorge Dinis-Oliveira, Sara Ricardo
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/25/1/323
_version_ 1797358681619169280
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
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-08T15:05:35Z
publishDate 2023-12-01
publisher MDPI AG
record_format Article
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
work_keys_str_mv AT dianaluisaalmeidanunes enhancingimmunotherapyinovariancancertheemergingroleofmetforminandstatins
AT ricardosilvestre enhancingimmunotherapyinovariancancertheemergingroleofmetforminandstatins
AT ricardojorgedinisoliveira enhancingimmunotherapyinovariancancertheemergingroleofmetforminandstatins
AT sararicardo enhancingimmunotherapyinovariancancertheemergingroleofmetforminandstatins