GIRARDINI BROVELLI Javier Enrique
Repositioning metformin and propranolol for colorectal and triple negative breast cancers treatment
ANSELMINO, LUCIANO; BAGLIONI, MARÍA VIRGINIA; MALIZIA, FLORENCIA; CESATTI LALUCE, NAHUEL; BORINI ETICHETTI, CARLA M; MARTINEZ MARIGNAC VL; ROZADOS, VIVIANA; SCHAROVSKY, OLGA GRACIELA; GIRARDINI, JAVIER; RICO, M. JOSE; MENACHO-MARQUEZ, MAURICIO
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 finding effective drugs with reduced side effects 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 difficult to treat. For both tumor types, available treatments are generally associated to severe side effects. In our work, we explored the effect of combining metformin and propranolol, two repositioned drugs, in both tumor types. We demonstrate that treatment affects viability, EMT transition and migratory potential of CRC cells as we described before for TNBC. We show that combined treatment affects all the steps leading to TNBC metastasis. Indeed, combined treatment is also effective 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 treatment without associated toxicity.