Metformin induces a fasting- and antifolate-mimicking modification of systemic host metabolism in breast cancer patients

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 r...

Descripción completa

Detalles Bibliográficos
Autores: 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.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/171561
Acceso en línea:https://hdl.handle.net/2445/171561
Access Level:acceso abierto
Palabra clave:Càncer de mama
Nutrició
Breast cancer
Nutrition
Descripción
Sumario: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.

Similares en LA Referencia