preprints.org > medicine and pharmacology > oncology and oncogenics > doi: 10.20944/preprints202212.0399.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 20 December 2022 / Approved: 21 December 2022 / Online: 21 December 2022 (10:05:50 CET)

Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) and lipids are strongly manipulated. After observing selective anticancer activity in vitro, we prepared five artificial diets and evaluated their anticancer activity in a challenging model of metastatic TNBC. The model was established by injecting 4T1 murine TNBC cells into the tail vein of immunocompetent BALB/cAnNRj mice. First-line drugs doxorubicin and capecitabine were used as positive controls. AA manipulation led to modest improvements in mice survival when the levels or lipids were normal. Reducing lipid levels to 1% markedly improved the activity of several diets with different AA content. Mice fed the artificial diets as monotherapy lived longer than mice treated with doxorubicin and capecitabine. An artificial diet without 10 non-essential AAs, with reduced levels of essential AAs, and with 1% lipids improved the survival not only of mice with TNBC but also of mice with other types of metastatic cancers.

Amino acids, lipids, diet, low-fat diet, cancer therapy, cancer metabolism, triple-negative breast cancer, lung cancer, melanoma, colorectal cancer, ovarian cancer, metastasis

Medicine and Pharmacology, Oncology and Oncogenics

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