Co-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden
Abstract Patients with metastatic breast cancer face reduced quality of life and increased mortality rates, necessitating more effective anti-cancer strategies. Building on previous research that identified metastatic-niche-specific metabolic vulnerabilities, we investigated how a ketogenic diet enh...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-024-00715-6 |
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| author | Qianying Zuo Jin Young Yoo Erik R. Nelson Matthew J. Sikora Rebecca B. Riggins Zeynep Madak-Erdogan |
| author_facet | Qianying Zuo Jin Young Yoo Erik R. Nelson Matthew J. Sikora Rebecca B. Riggins Zeynep Madak-Erdogan |
| author_sort | Qianying Zuo |
| collection | DOAJ |
| description | Abstract Patients with metastatic breast cancer face reduced quality of life and increased mortality rates, necessitating more effective anti-cancer strategies. Building on previous research that identified metastatic-niche-specific metabolic vulnerabilities, we investigated how a ketogenic diet enhances estrogen receptor (ER)-positive liver metastatic breast cancer’s response to Fulvestrant (Fulv) treatment. Using in vitro cell lines and in vivo xenograft metastasis mouse models, we examined the molecular mechanisms of combining ER targeting with a ketogenic diet. We found that Fulv treatment downregulates the ketogenesis pathway enzyme OXCT1, leading to β-hydroxybutyrate accumulation and decreased tumor cell viability. We also explored interactions between glucose, palmitic acid, and β-hydroxybutyric acid. These findings establish the molecular basis and clinical potential of a ketogenic diet to enhance Fulv efficacy in patients with ER+ liver metastatic breast cancer, potentially improving survival outcomes and quality of life in this population. |
| format | Article |
| id | doaj-art-2c594bb773de4b029ae779abac0b6af9 |
| institution | Kabale University |
| issn | 2374-4677 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj-art-2c594bb773de4b029ae779abac0b6af92025-01-19T12:33:39ZengNature Portfolionpj Breast Cancer2374-46772025-01-0111111310.1038/s41523-024-00715-6Co-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burdenQianying Zuo0Jin Young Yoo1Erik R. Nelson2Matthew J. Sikora3Rebecca B. Riggins4Zeynep Madak-Erdogan5Department of Food Science and Human Nutrition, University of Illinois at Urbana-ChampaignDepartment of Food Science and Human Nutrition, University of Illinois at Urbana-ChampaignDepartment of Molecular and Integrative Physiology, University of Illinois Urbana-ChampaignDepartment of Pathology, University of Colorado Anschutz Medical CampusDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown UniversityDepartment of Food Science and Human Nutrition, University of Illinois at Urbana-ChampaignAbstract Patients with metastatic breast cancer face reduced quality of life and increased mortality rates, necessitating more effective anti-cancer strategies. Building on previous research that identified metastatic-niche-specific metabolic vulnerabilities, we investigated how a ketogenic diet enhances estrogen receptor (ER)-positive liver metastatic breast cancer’s response to Fulvestrant (Fulv) treatment. Using in vitro cell lines and in vivo xenograft metastasis mouse models, we examined the molecular mechanisms of combining ER targeting with a ketogenic diet. We found that Fulv treatment downregulates the ketogenesis pathway enzyme OXCT1, leading to β-hydroxybutyrate accumulation and decreased tumor cell viability. We also explored interactions between glucose, palmitic acid, and β-hydroxybutyric acid. These findings establish the molecular basis and clinical potential of a ketogenic diet to enhance Fulv efficacy in patients with ER+ liver metastatic breast cancer, potentially improving survival outcomes and quality of life in this population.https://doi.org/10.1038/s41523-024-00715-6 |
| spellingShingle | Qianying Zuo Jin Young Yoo Erik R. Nelson Matthew J. Sikora Rebecca B. Riggins Zeynep Madak-Erdogan Co-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden npj Breast Cancer |
| title | Co-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden |
| title_full | Co-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden |
| title_fullStr | Co-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden |
| title_full_unstemmed | Co-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden |
| title_short | Co-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden |
| title_sort | co targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden |
| url | https://doi.org/10.1038/s41523-024-00715-6 |
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