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

BRUNI, SOFIA; DE MARTINO, MARA; PROIETTI, CECILA JAZMÍN; ELIZALDE, PATRICIA V.; SCHILLACI, ROXANA; MERCOGLIANO, MARÍA FLORENCIA

Mar del Plata

Congreso; LX Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

Sociedad Argentina de Investigación Clínica (SAIC)

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