2026-04-14T09:12:00Zhttps://recercat.cat/oai/request
oai:recercat.cat:10256/215992025-02-04T06:50:26Zcom_2072_452955com_2072_2054col_2072_453079
RECERCAT author Cuyàs, Elisabet author Fernández-Arroyo, Salvador author Buxó Pujolràs, Maria author Pernas, Sonia author Dorca Ribugent, Joan author Álvarez, Isabel author Martínez, Susana author Pérez-Garcia, Jose Manuel author Batista López, Norberto author Rodríguez Sánchez, César A. author Amillano, Kepa author Domínguez, Severina author Luque, Maria author Morilla, Idoia author Stradella, Agostina author Viñas, Gemma author Cortés, Javier author Verdura, Sara author Brunet i Vidal, Joan author López Bonet, Eugeni author Garcia, Margarita author Saidani, Samiha author Joven, Jorge author Martin Castillo, Begoña author Menéndez Menéndez, Javier Abel 2019-05-09 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 Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Cèl·lules canceroses Mama -- Càncer Breast -- Cancer Càncer -- Tractament Cancer -- Treatment Metformin induces a fasting- and antifolate-mimicking modification of systemic host metabolism in breast cancer patients info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion