Vitamin D analogues exhibit antineoplastic activity in breast cancer patient-derived xenograft cells.

FERRONATO, M.J.; NADAL SERRANO, M.; ARENAS LAHUERTA, E.J.; BERNADÓ MORALES, C.; PAOLILLO, G.; MARTINEZ-SABADELL ALIGUER, A.; MASCARÓ, M.; VITALE, C. ; FALL, Y.; ARRIBAS, J.; FACCHINETTI, M.M.; CURINO, A.C.

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2021

0960-0760

spite advances in breast cancer (BC) treatment, its mortality remains high due tointrinsic or acquired resistance to therapy. Several ongoing efforts are being made todevelop 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 thatthe non-hypercalcemic vitamin D analogues EM1 and UVB1 display antitumor effectsin preclinical studies employing conventional cell lines and animal models developedfrom these cells. In this work, we explored the antitumor effects of EM1 and UVB1employing BC cells derived from patient-derived xenografts (PDXs), which are apowerful preclinical tool for testing new drugs. We demonstrated that the analoguesreduced the viability of HER2-positive and Triple Negative BC-PDXs. Moreover, usingan in vitro model of acquired resistance to Trastuzumab-emtansine, UVB1 displayedanti-proliferative actions under 2D and 3D culture conditions. It inhibited both formationand growth of established organoids. In addition, a direct correlation between UVB1antitumor effects and VDR expression in PDXs was found. In conclusion, all the resultsreinforce the potential use of these vitamin D analogues as antitumor agents to treatHER2-positive and Triple Negative BC.