Calcitriol analogue EM1 as promising antimetastatic agent in TNBC

IBARRA, AGUSTINA; GANDINI, NORBERTO ARIEL; MASCARÓ, MARILINA; FERRONATO, MARÍA JULIA; CURINO, ALEJANDRO CARLOS; FERMENTO, MARIA EUGENIA; GRIOLI, SILVINA MARIELA; GUEVARA, JOSEFINA ALEJANDRA; ALONSO, ELIANA NOELIA; COLÓ, GEORGINA PAMELA; FACCHINETTI, MARÍA MARTA

Congreso; LXIII Reunión Anual de SAIC; 2018

The Triple negative breast cancer (TNBC), that lacks hormone receptors and epidermal growth factor receptor HER2 as therapeutic targets, it does not respond to conventional therapies. Until now, the only treatment are cytotoxic drugs such as taxanes, but this therapy is limited in terms of extending the survival and improving the life quality of the patient.The vitamin D receptor (VDR) is a nuclear transcription factor whose natural ligand, calcitriol, has antitumor activity. Unfortunately, its usefulness is limited by its hypercalcemic effects.Our hypothesis is that the analogue of calcitriol, EM1, has synergistic effect with Paclitaxel in TNBC without exerting additional toxicity. This would allow to use lower doses of cytotoxic chemotherapy, with the consequent reduction of adverse effects. Also, EM1 in combination with Paclitaxel could minimize or slow the development of resistance to chemotherapeutic agents.We observed that EM1 decreases viability in the TNBC murine line 4T1(p