info:eu-repo/semantics/article
Vitamin D analogues exhibit antineoplastic activity in breast cancer patient-derived xenograft cells
Fecha
2020-08-09Registro en:
Ferronato, María Julia; Nadal, Serrano Mercedes; Arenas Lahuerta, Enrique Javier; Morales, Cristina Bernadó; Paolillo, Giuliana; et al.; Vitamin D analogues exhibit antineoplastic activity in breast cancer patient-derived xenograft cells; Pergamon-Elsevier Science Ltd; Journal of Steroid Biochemistry and Molecular Biology; 9-8-2020; 1-28
0960-0760
1879-1220
CONICET Digital
CONICET
Autor
Ferronato, María Julia
Nadal, Serrano Mercedes
Arenas Lahuerta, Enrique Javier
Morales, Cristina Bernadó
Paolillo, Giuliana
Martinez Sabadell, Aliguer Alex
Mascaró, Marilina
Vitale, Cristian Alejandro
Fall, Yagamare
Arribas, Joaquín
Facchinetti, María Marta
Curino, Alejandro Carlos
Resumen
Despite advances in breast cancer (BC) treatment, its mortality remains high due to intrinsic or acquired resistance to therapy. Several ongoing efforts are being made to develop novel drugs to treat this pathology with the aim to overcome resistance, prolong patient survival and improve their quality of life. We have previously shown that the non-hypercalcemic vitamin D analogues EM1 and UVB1 display antitumor effects in preclinical studies employing conventional cell lines and animal models developed from these cells. In this work, we explored the antitumor effects of EM1 and UVB1 employing BC cells derived from patient-derived xenografts (PDXs), which are a powerful preclinical tool for testing new drugs. We demonstrated that the analogues reduced the viability of HER2-positive and Triple Negative BC-PDXs. Moreover, using an in vitro model of acquired resistance to Trastuzumab-emtansine, UVB1 displayed anti-proliferative actions under 2D and 3D culture conditions. It inhibited both formation and growth of established organoids. In addition, a direct correlation between UVB1 antitumor effects and VDR expression in PDXs was found. In conclusion, all the results reinforce the potential use of these vitamin D analogues as antitumor agents to treat HER2-positive and Triple Negative BC.