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Published version

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2019-01-15

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cc by (c) Cuyàs et al., 2019
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/171561

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

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https://doi.org/10.18632/aging.101960

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.

Subject

Càncer de mama, Nutrició

Subject (English)

Breast cancer, Nutrition

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citation

CUYÀS, Elisabet, et al. Metformin induces a fasting- and antifolate-mimicking modification of systemic host metabolism in breast cancer patients. Aging-us. 2019. Vol. 11, num. 9, pags. 2874-2888. [consulted: 8 of August of 2026]. Available at: https://hdl.handle.net/2445/171561

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