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

Autores
Mainetti, Leandro Ernesto; Rico, Maria Jose; Kaufman, Cintia Daniela; Grillo, Monica Carolina; Guercetti, Julian; Baglioni, María Virginia; del Giúdice, Antonela; Capitani, María Celeste; Fusini, Matías; Rozados, Viviana Rosa; Scharovsky, Olga Graciela
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Mainetti, Leandro Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Rico, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Kaufman, Cintia Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Grillo, Monica Carolina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Guercetti, Julian. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Baglioni, María Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: del Giúdice, Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Capitani, María Celeste. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Fusini, Matías. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Rozados, Viviana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Scharovsky, Olga Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Metronomics Global Health Initiative; Francia
Materia
CYCLOPHOSPHAMIDE
DRUG REPURPOSING
LOSARTAN
MAMMARY CANCER
METRONOMIC CHEMOTHERAPY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/174946
Acceder
id CONICETDig_9fdbce68829e77344200a7306d83e53f
oai_identifier_str oai:ri.conicet.gov.ar:11336/174946
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer modelsMainetti, Leandro ErnestoRico, Maria JoseKaufman, Cintia DanielaGrillo, Monica CarolinaGuercetti, JulianBaglioni, María Virginiadel Giúdice, AntonelaCapitani, María CelesteFusini, MatíasRozados, Viviana RosaScharovsky, Olga GracielaCYCLOPHOSPHAMIDEDRUG REPURPOSINGLOSARTANMAMMARY CANCERMETRONOMIC CHEMOTHERAPYhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Metronomic 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.Fil: Mainetti, Leandro Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Rico, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Kaufman, Cintia Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Grillo, Monica Carolina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Guercetti, Julian. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Baglioni, María Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: del Giúdice, Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Capitani, María Celeste. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Fusini, Matías. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Rozados, Viviana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Scharovsky, Olga Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Metronomics Global Health Initiative; FranciaImpact Journals2020-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/174946Mainetti, Leandro Ernesto; Rico, Maria Jose; Kaufman, Cintia Daniela; Grillo, Monica Carolina; Guercetti, Julian; et al.; Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models; Impact Journals; Oncotarget; 11; 32; 8-2020; 3048-30601949-2553CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.oncotarget.com/article/27694/text/info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.27694info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:02:12Zoai:ri.conicet.gov.ar:11336/174946instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:02:12.739CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 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
spellingShingle Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models
Mainetti, Leandro Ernesto
CYCLOPHOSPHAMIDE
DRUG REPURPOSING
LOSARTAN
MAMMARY CANCER
METRONOMIC CHEMOTHERAPY
title_short 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_sort Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models
dc.creator.none.fl_str_mv Mainetti, Leandro Ernesto
Rico, Maria Jose
Kaufman, Cintia Daniela
Grillo, Monica Carolina
Guercetti, Julian
Baglioni, María Virginia
del Giúdice, Antonela
Capitani, María Celeste
Fusini, Matías
Rozados, Viviana Rosa
Scharovsky, Olga Graciela
author Mainetti, Leandro Ernesto
author_facet Mainetti, Leandro Ernesto
Rico, Maria Jose
Kaufman, Cintia Daniela
Grillo, Monica Carolina
Guercetti, Julian
Baglioni, María Virginia
del Giúdice, Antonela
Capitani, María Celeste
Fusini, Matías
Rozados, Viviana Rosa
Scharovsky, Olga Graciela
author_role author
author2 Rico, Maria Jose
Kaufman, Cintia Daniela
Grillo, Monica Carolina
Guercetti, Julian
Baglioni, María Virginia
del Giúdice, Antonela
Capitani, María Celeste
Fusini, Matías
Rozados, Viviana Rosa
Scharovsky, Olga Graciela
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CYCLOPHOSPHAMIDE
DRUG REPURPOSING
LOSARTAN
MAMMARY CANCER
METRONOMIC CHEMOTHERAPY
topic CYCLOPHOSPHAMIDE
DRUG REPURPOSING
LOSARTAN
MAMMARY CANCER
METRONOMIC CHEMOTHERAPY
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Mainetti, Leandro Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Rico, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Kaufman, Cintia Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Grillo, Monica Carolina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Guercetti, Julian. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Baglioni, María Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: del Giúdice, Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Capitani, María Celeste. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Fusini, Matías. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Rozados, Viviana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Fil: Scharovsky, Olga Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Metronomics Global Health Initiative; Francia
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.
publishDate 2020
dc.date.none.fl_str_mv 2020-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/174946
Mainetti, Leandro Ernesto; Rico, Maria Jose; Kaufman, Cintia Daniela; Grillo, Monica Carolina; Guercetti, Julian; et al.; Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models; Impact Journals; Oncotarget; 11; 32; 8-2020; 3048-3060
1949-2553
CONICET Digital
CONICET
url http://hdl.handle.net/11336/174946
identifier_str_mv Mainetti, Leandro Ernesto; Rico, Maria Jose; Kaufman, Cintia Daniela; Grillo, Monica Carolina; Guercetti, Julian; et al.; Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models; Impact Journals; Oncotarget; 11; 32; 8-2020; 3048-3060
1949-2553
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.oncotarget.com/article/27694/text/
info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.27694
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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