Synergistic combination of paclitaxel with novel non-hypercalcemic calcitriol analog EM1 against triple-negative breast cancer cell: new mechanism of action

GUEVARA, J.A.; IBARRA, A.; FERRONATO, M.J.; ALONSO, E.N.; FERMENTO, M.E.; COLÓ, G.P.; VITALE, C.; MASCARÓ, E.; QUEVEDO, M.A.; FACCHINETTI, M.M.; CURINO, A.C.

Mar del Plata

Otro; LXVII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2022

SAIC

Triple-negative breast cancer (TNBC) is currently treated with cytotoxic drugs such as paclitaxel (PTX) since it lacks targeted therapies, although it shows limitations in extending patient survival. The known mechanism of action of PTX is binding to β-tubulin and inducing apoptosis. The vitamin D receptor (VDR) is expressed in different tissues, including TNBC. Calcitriol, its natural ligand, shows antitumor activity, but its usefulness is limited by the hypercalcemia it causes at antitumor doses. Reports suggest that PTX shows synergism when combined with calcitriol. The aim of this work is to combine PTX and non-hypercalcemic VDR analogs synthesized by our group, to study the potential synergism of the calcitriol analog EM1 with the cytotoxic PTX.EM1 in combination with PTX (EM1+PTX), showed a synergistic effect on the viability of 4T1 and MDAMB231 TNBC cell lines (p