TNF ALPHA INDUCES MULTIRESISTANCE TO HER2-TARGETED THERAPIES IN BREAST CANCER

PROIETTI CJ; MERCOGLIANO MF; DE MARTINO M; SCHILLACI R; BRUNI S; ELIZALDE PV

Congreso; LXI Reunión Anual de la SAIC; 2016

HER2 positive (HER2+) is a breast cancer (BC) subtype characterizedby HER2 overexpression/amplification and affects ~15%of BC patients, who receive trastuzumab (T), an anti-HER2 mono -clonal antibody, but resistance events hamper its clinical benefitsin 40-60% of the cases. We have demonstrated that TNFα overexpressionturned T-sensitive cells and tumors into resistant ones,and this resistance mechanism was mediated by upregulation ofmucin 4 (MUC4). Nowadays there are new anti-HER2 therapiessuch as the dual tyrosine kinase inhibitor lapatinib (L) and antibodies,like T-DM1 and pertuzumab (P). The aim of this work was toexplore whether TNF and TNF-induced MUC4 expression play arole as a multiresistance factor to these new therapies.We performedcell proliferation assays by cell count and by 3H-thymid ineincorporation using T-sensitive (C) and T-resistant BT-474 cells(T2), the latter engineered to overexpress TNF. The combinationof T+P (10 μg/ml each) was more effective that T alone in C cells(?65.7% and -30.6% respectively, and, P