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Abstract
Discovery of new drugs for cancer treatment is an expensive and time-consuming process and the percentage of drugs reaching the clinic remains quite low.Drug repositioning refers to the identification and development of new uses for existing drugs and represents an alternative drug development strategy.In this work, we evaluated the antitumor effect of metronomic treatment with a combination of two repositioned drugs, metformin and propranolol, in triple negative breast cancer models.By in vitro studies with five different breast cancer derived cells, we observed that combined treatment decreased proliferation (P < 0.001), mitochondrial activity (P < 0.001), migration (P < 0.001) and invasion (P < 0.001). In vivo studies in immunocompetent mice confirmed the potential of this combination in reducing tumor growth (P < 0.001) and preventing metastasis (P < 0.05).Taken together our results suggest that metformin plus propranolol combined treatment might be beneficial for triple negative breast cancer control, with no symptoms of toxicity.
Highlights
IntroductionTriple-negative breast cancer (TNBC) exhibit characteristics distinct from the others, as they are aggressive, frequently recur and become metastatic
Among breast cancer subtypes, triple-negative breast cancer (TNBC) exhibit characteristics distinct from the others, as they are aggressive, frequently recur and become metastatic
We evaluated the antitumor effect of metronomic treatment with a combination of two repositioned drugs, metformin and propranolol, in triple negative breast cancer models
Summary
Triple-negative breast cancer (TNBC) exhibit characteristics distinct from the others, as they are aggressive, frequently recur and become metastatic. Dynamics and toxicities, and because most repositioned drugs are available at low cost, normally as generics [2] which provides an opportunity to bypass partially the early costs and time associated to new drugs development. This is a particular issue for low-income countries, where the availability of drugs for cancer treatment is very limited and restricted to some essential cytotoxic drugs and cost is a major factor in influencing access to cancer therapies [3]. Developed and approved drugs that showed an anti-cancer opportunity for therapy can be administered orally, on daily basis, in a metronomic fashion
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