Repositioning metformin and propranolol for colorectal and triple negative breast cancers treatment

Drug repositioning refers to new uses for existing drugs outside the scope of the original medical indications. This approach fastens the process of drug development allowing fnding efective drugs with reduced side efects and lower costs. Colorectal cancer (CRC) is often diagnosed at advanced stages, when the probability of chemotherapy resistance is higher. Triple negative breast cancer (TNBC) is the most aggressive type of breast cancer, highly metastatic and difcult to treat. For both tumor types, available treatments are generally associated to severe side efects. In our work, we explored the efect of combining metformin and propranolol, two repositioned drugs, in both tumor types. We demonstrate that treatment afects viability, epithelial-mesenchymal transition and migratory potential of CRC cells as we described before for TNBC. We show that combined treatment afects diferent steps leading to metastasis in TNBC. Moreover, combined treatment is also efective preventing the development of 5-FU resistant CRC. Our data suggest that combination of metformin and propranolol could be useful as a putative adjuvant treatment for both TNBC and CRC and an alternative for chemo-resistant CRC, providing a low-cost alternative therapy without associated toxicity.