Novel therapeutic approaches with repositioned drugs for triple negative breast cancer treatment

BAGLIONI MV,; REYNOSO GS, ; ANSELMINO LE,; CESATTI LALUCE N, ; MAINETTI LE, ; ROZADOS VR, ; SCHAROVSKY OG, ; MENACHO MARQUEZ MA, ; RICO MJ

Congreso; SAB, SAIC, SAI, SAFIS.; 2020

Triple negative breast cancer (TNBC) is a particularly aggressivetype of breast cancer with poor prognosis and limited therapeuticoptions. Drug repositioning refers to new uses outside the scopeof the original medical indications for existing drugs or compounds.Metformin (M) is an antidiabetic, propranolol (P) is a β-blocker, chloroquine(CQ) is used to treat malaria. We found that M+P combinationcould be effective for triple negative breast cancer (TNBC)treatment. Our aim was to widen the knowledge of the mechanismsresponsible for the effects of M+P treatment and to study the effectof other repositioned drugs combinations on TNBC. We performedan in vitro screening of drugs under reposition on TNBC cells and determinedthat M+P and CQ+P were particularly efficient in reducingproliferation. They showed synergistic effect, affecting significantlyapoptosis. M+P reduced phospho Erk levels after serum inductionbut did not affect the expression levels of the epithelial markersβ-catenin and E-cadherin. In vivo treatment with M(2g/l)+P(25mg/l)in 4T1 and M-406 models reduced tumor growth and metastasisdevelopment, while CQ+P did not show antitumor effect. Evaluationof the effect of M+P on immune cells revealed an increase inintratumor M-406 Tregs (P