2026-04-14T09:39:19Zhttps://recercat.cat/oai/request

oai:recercat.cat:10256/215992025-02-04T06:50:26Zcom_2072_452955com_2072_2054col_2072_453079

Metformin induces a fasting- and antifolate-mimicking modification of systemic host metabolism in breast cancer patients Cuyàs, Elisabet Fernández-Arroyo, Salvador Buxó Pujolràs, Maria Pernas, Sonia Dorca Ribugent, Joan Álvarez, Isabel Martínez, Susana Pérez-Garcia, Jose Manuel Batista López, Norberto Rodríguez Sánchez, César A. Amillano, Kepa Domínguez, Severina Luque, Maria Morilla, Idoia Stradella, Agostina Viñas, Gemma Cortés, Javier Verdura, Sara Brunet i Vidal, Joan López Bonet, Eugeni Garcia, Margarita Saidani, Samiha Joven, Jorge Martin Castillo, Begoña Menéndez Menéndez, Javier Abel Cèl·lules canceroses Mama -- Càncer Breast -- Cancer Càncer -- Tractament Cancer -- Treatment Certain dietary interventions might improve the therapeutic index of cancer treatments. An alternative to the 'drug plus diet' approach is the pharmacological reproduction of the metabolic traits of such diets. Here we explored the impact of adding metformin to an established therapeutic regimen on the systemic host metabolism of cancer patients. A panel of 11 serum metabolites including markers of mitochondrial function and intermediates/products of folate-dependent one-carbon metabolism were measured in paired baseline and post-treatment sera obtained from HER2-positive breast cancer patients randomized to receive either metformin combined with neoadjuvant chemotherapy and trastuzumab or an equivalent regimen without metformin. Metabolite profiles revealed a significant increase of the ketone body β-hydroxybutyrate and of the TCA intermediate α-ketoglutarate in the metformin-containing arm. A significant relationship was found between the follow-up levels of homocysteine and the ability of treatment arms to achieve a pathological complete response (pCR). In the metformin-containing arm, patients with significant elevations of homocysteine tended to have a higher probability of pCR. The addition of metformin to an established anti-cancer therapeutic regimen causes a fasting-mimicking modification of systemic host metabolism. Circulating homocysteine could be explored as a clinical pharmacodynamic biomarker linking the antifolate-like activity of metformin and biological tumor response 2019-05-09 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/10256/21599 eng info:eu-repo/semantics/altIdentifier/doi/10.18632/aging.101960 info:eu-repo/semantics/altIdentifier/issn/1945-4589 info:eu-repo/semantics/altIdentifier/eissn/1945-4589 Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess 15 p. application/pdf Impact Journals Aging, 2019, vol. 11, num. 9, p. 2874-2888 Articles publicats (IdIBGi) Cuyàs, Elisabet Fernández-Arroyo S Buxó Pujolràs, Maria Pernas, Sonia Dorca, Joan Álvarez, Isabel Martínez, Susana Pérez-Garcia, Jose Manuel Batista López, Norberto Rodríguez Sánchez, César A. Amillano, Kepa Domínguez, Severina Luque, Maria Morilla, Idoia Stradella, Agostina Viñas, Gemma Cortés, Javier Verdura, Sara Brunet i Vidal, Joan López Bonet, Eugeni Garcia, Margarita Saidani, Samiha Joven, Jorge Martin Castillo, Begoña Menéndez Menéndez, Javier Abel 2019 Metformin induces a fasting- and antifolate-mimicking modification of systemic host metabolism in breast cancer patients Aging 11 9 2874 2888