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Title: Metformin induces a fasting- and antifolate-mimicking modification of systemic host metabolism in breast cancer patients
Author: Cuyàs, Elisabet
Fernández Arroyo, Salvador
Buxó, Maria
Pernas, Sònia
Dorca, Joan
Álvarez, Isabel
Martínez, Susana
Pérez García, José 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, Joan
López Bonet, Eugeni
Garcia, Margarita
Saidani, Samiha
Joven, Jorge
Martin Castillo, Begoña
Menendez, Javier A.
Keywords: Càncer de mama
Breast cancer
Issue Date: 15-Jan-2019
Publisher: Impact Journals
Abstract: 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 mitochondria! 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 beta-hydroxybutyrate and of the TCA intermediate alpha-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 anticancer 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.
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It is part of: Aging-us, 2019, vol. 11, num. 9, p. 2874-2888
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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