Preclinical studies of the combination of EM1 calcitriol analogue with Paclitaxel in TNBC

GUEVARA JA; IBARRA A; FERRONATO MJ; ALONSO EN; GANDINI NA; FERMENTO ME; COLO GP; MASCARO M; GRIOLI SM; FACCHINETTI MM; CURINO AC

Mar del Plata

Congreso; LXIII Reunion Anual de la Sociedad Argentina de Investigacion Clinica; 2018

Sociedad Argentina de Investigacion Clinica

Triple negative breast cancer (TNBC) does not respond to current targeted therapies as it lacks the expression of hormone receptors and epidermal growth factor receptor HER2. Therefore, current treatment options include cytotoxic drugs such as taxanes, which are limited in terms of extending patient survival or improving patient?s quality of life. The vitamin D receptor is a nuclear transcription factor whose natural ligand, calcitriol, has antitumor activity. Unfortunately, calcitriol anticancer utility is limited by its hypercalcemic effects and thus, vitamin D analogues are being developed to try to solve this problem. We hypothesize 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, this combination could minimize or slow the development of resistance to chemotherapeutic agents. We first studied the activity of EM1 on cell count and observed that EM1 strongly decreases the viability of the 4T1 TNBC murine cell line (p