Abstract
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.
Highlights
Cancer is the second-leading cause of death behind heart disease [1], accounting for an estimation of 9.6 million deaths in 2018 [2].Biomolecules 2018, 8, 175; doi:10.3390/biom8040175 www.mdpi.com/journal/biomoleculesWhen dealing with this disease, there are three important priorities, which are, in order of importance: prevention, early detection and total eradication
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It is important to note that high standard error of the mean (SEM) values were obtained, since the two experiments resulted in very different values
Summary
When dealing with this disease, there are three important priorities, which are, in order of importance: prevention, early detection and total eradication. Concerning pharmacotherapy, the ideal drug is one that selectively kills the neoplastic cells, minimizing adverse effects. Intense pharmacological research is being made about oncological therapy, originating an explosion of costs. Despite this big investment, there is little output for a huge pharma research and development spending. There is a requirement for more effective cancer drugs. To face this problem, an interesting approach named drug repurposing is being increasingly applied [7]. Highlighting the importance of this approach, the global market for drug repurposing reached €20.7 billion in 2015 and is projected to reach €26.6 billion by 2020 [8]
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