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Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models

Metronomic chemotherapy refers to the minimum biologically effective doses of a chemotherapy agent given as a continuous regimen without extended rest periods. Drug repurposing is defined as the use of an already known drug for a new medical indication, different from the original one. In oncology t...

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Autores principales: Mainetti, Leandro E., Rico, María José, Kaufman, Cintia Daniela, Grillo, Monica Carolina, Guercetti, Julian, Baglioni, María Virginia, Del Giúdice, Antonela, Capitani, Maria Celeste, Fusini, Matias, Rozados, Viviana Rosa, Scharovsky, O. Graciela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429183/
https://www.ncbi.nlm.nih.gov/pubmed/32850009
http://dx.doi.org/10.18632/oncotarget.27694
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author Mainetti, Leandro E.
Rico, María José
Kaufman, Cintia Daniela
Grillo, Monica Carolina
Guercetti, Julian
Baglioni, María Virginia
Del Giúdice, Antonela
Capitani, Maria Celeste
Fusini, Matias
Rozados, Viviana Rosa
Scharovsky, O. Graciela
author_facet Mainetti, Leandro E.
Rico, María José
Kaufman, Cintia Daniela
Grillo, Monica Carolina
Guercetti, Julian
Baglioni, María Virginia
Del Giúdice, Antonela
Capitani, Maria Celeste
Fusini, Matias
Rozados, Viviana Rosa
Scharovsky, O. Graciela
author_sort Mainetti, Leandro E.
collection PubMed
description Metronomic chemotherapy refers to the minimum biologically effective doses of a chemotherapy agent given as a continuous regimen without extended rest periods. Drug repurposing is defined as the use of an already known drug for a new medical indication, different from the original one. In oncology the combination of these two therapeutic approaches is called “Metronomics”. The aim of this work is to evaluate the therapeutic effect of cyclophosphamide in a metronomic schedule in combination with the repurposed drug losartan in two genetically different mice models of triple negative breast cancer. Our findings showed that adding losartan to metronomic cyclophosphamide significantly improved the therapeutic outcome. In both models the combined treatment increased the mice’s survival without sings of toxicity. Moreover, we elucidated some of the mechanisms of action involved, which include a decrease of intratumor hypoxia, stimulation of the immune response and remodeling of the tumor microenvironment. The remarkable therapeutic effect, the lack of toxicity, the low cost of the drugs and its oral administration, strongly suggest its translation to the clinical setting in the near future.
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spelling pubmed-74291832020-08-25 Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models Mainetti, Leandro E. Rico, María José Kaufman, Cintia Daniela Grillo, Monica Carolina Guercetti, Julian Baglioni, María Virginia Del Giúdice, Antonela Capitani, Maria Celeste Fusini, Matias Rozados, Viviana Rosa Scharovsky, O. Graciela Oncotarget Research Paper Metronomic chemotherapy refers to the minimum biologically effective doses of a chemotherapy agent given as a continuous regimen without extended rest periods. Drug repurposing is defined as the use of an already known drug for a new medical indication, different from the original one. In oncology the combination of these two therapeutic approaches is called “Metronomics”. The aim of this work is to evaluate the therapeutic effect of cyclophosphamide in a metronomic schedule in combination with the repurposed drug losartan in two genetically different mice models of triple negative breast cancer. Our findings showed that adding losartan to metronomic cyclophosphamide significantly improved the therapeutic outcome. In both models the combined treatment increased the mice’s survival without sings of toxicity. Moreover, we elucidated some of the mechanisms of action involved, which include a decrease of intratumor hypoxia, stimulation of the immune response and remodeling of the tumor microenvironment. The remarkable therapeutic effect, the lack of toxicity, the low cost of the drugs and its oral administration, strongly suggest its translation to the clinical setting in the near future. Impact Journals LLC 2020-08-11 /pmc/articles/PMC7429183/ /pubmed/32850009 http://dx.doi.org/10.18632/oncotarget.27694 Text en http://creativecommons.org/licenses/by/3.0/ Copyright: Mainetti et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Mainetti, Leandro E.
Rico, María José
Kaufman, Cintia Daniela
Grillo, Monica Carolina
Guercetti, Julian
Baglioni, María Virginia
Del Giúdice, Antonela
Capitani, Maria Celeste
Fusini, Matias
Rozados, Viviana Rosa
Scharovsky, O. Graciela
Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models
title Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models
title_full Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models
title_fullStr Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models
title_full_unstemmed Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models
title_short Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models
title_sort losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429183/
https://www.ncbi.nlm.nih.gov/pubmed/32850009
http://dx.doi.org/10.18632/oncotarget.27694
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