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Study of New Therapeutic Strategies to Combat Breast Cancer Using Drug Combinations

Cancer is a disease that affects and kills millions of people worldwide. Breast cancer, especially, has a high incidence and mortality, and is challenging to treat. Due to its high impact on the health sector, oncological therapy is the subject of an intense and very expensive research. To improve t...

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Autores principales: Correia, Ana, Silva, Dany, Correia, Alexandra, Vilanova, Manuel, Gärtner, Fátima, Vale, Nuno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315516/
https://www.ncbi.nlm.nih.gov/pubmed/30558247
http://dx.doi.org/10.3390/biom8040175
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author Correia, Ana
Silva, Dany
Correia, Alexandra
Vilanova, Manuel
Gärtner, Fátima
Vale, Nuno
author_facet Correia, Ana
Silva, Dany
Correia, Alexandra
Vilanova, Manuel
Gärtner, Fátima
Vale, Nuno
author_sort Correia, Ana
collection PubMed
description Cancer is a disease that affects and kills millions of people worldwide. Breast cancer, especially, has a high incidence and mortality, and is challenging to treat. Due to its high impact on the health sector, oncological therapy is the subject of an intense and very expensive research. To improve this therapy and reduce its costs, strategies such as drug repurposing and drug combinations have been extensively studied. Drug repurposing means giving new usefulness to drugs which are approved for the therapy of various diseases, but, in this case, are not approved for cancer therapy. On the other hand, the purpose of combining drugs is that the response that is obtained is more advantageous than the response obtained by the single drugs. Using drugs with potential to be repurposed, combined with 5-fluorouracil, the aim of this project was to investigate whether this combination led to therapeutic benefits, comparing with the isolated drugs. We started with a screening of the most promising drugs, with verapamil and itraconazole being chosen. Several cellular viability studies, cell death and proliferation studies, mainly in MCF-7 cells (Michigan Cancer Foundation-7, human breast adenocarcinoma cells) were performed. Studies were also carried out to understand the effect of the drugs at the level of possible therapeutic resistance, evaluating the epithelial-mesenchymal transition. Combining all the results, the conclusion is that the combination of verapamil and itraconazole with 5-fluorouracil had benefits, mainly by decreasing cell viability and proliferation. Furthermore, the combination of itraconazole and 5-fluorouracil seemed to be the most effective, being an interesting focus in future studies.
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spelling pubmed-63155162019-01-10 Study of New Therapeutic Strategies to Combat Breast Cancer Using Drug Combinations Correia, Ana Silva, Dany Correia, Alexandra Vilanova, Manuel Gärtner, Fátima Vale, Nuno Biomolecules Article Cancer is a disease that affects and kills millions of people worldwide. Breast cancer, especially, has a high incidence and mortality, and is challenging to treat. Due to its high impact on the health sector, oncological therapy is the subject of an intense and very expensive research. To improve this therapy and reduce its costs, strategies such as drug repurposing and drug combinations have been extensively studied. Drug repurposing means giving new usefulness to drugs which are approved for the therapy of various diseases, but, in this case, are not approved for cancer therapy. On the other hand, the purpose of combining drugs is that the response that is obtained is more advantageous than the response obtained by the single drugs. Using drugs with potential to be repurposed, combined with 5-fluorouracil, the aim of this project was to investigate whether this combination led to therapeutic benefits, comparing with the isolated drugs. We started with a screening of the most promising drugs, with verapamil and itraconazole being chosen. Several cellular viability studies, cell death and proliferation studies, mainly in MCF-7 cells (Michigan Cancer Foundation-7, human breast adenocarcinoma cells) were performed. Studies were also carried out to understand the effect of the drugs at the level of possible therapeutic resistance, evaluating the epithelial-mesenchymal transition. Combining all the results, the conclusion is that the combination of verapamil and itraconazole with 5-fluorouracil had benefits, mainly by decreasing cell viability and proliferation. Furthermore, the combination of itraconazole and 5-fluorouracil seemed to be the most effective, being an interesting focus in future studies. MDPI 2018-12-14 /pmc/articles/PMC6315516/ /pubmed/30558247 http://dx.doi.org/10.3390/biom8040175 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Correia, Ana
Silva, Dany
Correia, Alexandra
Vilanova, Manuel
Gärtner, Fátima
Vale, Nuno
Study of New Therapeutic Strategies to Combat Breast Cancer Using Drug Combinations
title Study of New Therapeutic Strategies to Combat Breast Cancer Using Drug Combinations
title_full Study of New Therapeutic Strategies to Combat Breast Cancer Using Drug Combinations
title_fullStr Study of New Therapeutic Strategies to Combat Breast Cancer Using Drug Combinations
title_full_unstemmed Study of New Therapeutic Strategies to Combat Breast Cancer Using Drug Combinations
title_short Study of New Therapeutic Strategies to Combat Breast Cancer Using Drug Combinations
title_sort study of new therapeutic strategies to combat breast cancer using drug combinations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315516/
https://www.ncbi.nlm.nih.gov/pubmed/30558247
http://dx.doi.org/10.3390/biom8040175
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