MITOCHONDRIAL AEROBIC METABOLISM PLAYS A KEY ROLE IN HER2+ TRASTUZUMAB-RESISTANT BREAST CANCER TUMOR SPHEROIDS

TAPIA, IVANA; PERICO, DAVIDE; DE PALMA, ANTONELLA; WOLOS, VIRGINIA J; VILLAVERDE M.S; MAURI, PIER L; ROCCA, ; ABRIGO, M; SILVESTRE, ; FISZMAN G.L

Congreso; SAIC 2022; 2022

Breast cancer (BC) is the leading cause of death in women worldwide. Around 15-20% of BC tumors overexpress HER2, which is associated with poor disease-free survival. Targeted anti-HER2 therapies such as Trastuzumab (Tz), provide an option for these patients. However, ~60% of them acquire a resistant phenotype during the first year of treatment. In order to identify protein profiles associated with Tz resistance, a comparative proteomic study was performed. Two differential Tz response levels in a 3D culture model were mimicked using a HER2+ human mammary adenocarcinoma cell line (BT-474) and its derived resistant cell line developed in our laboratory (partial Responder Spheroids RS and non-Responder Spheroids n-RS, respectively). For 15 days both spheroids were treated with Tz (50 𝛍g/ml) (%inhibition, RS: 51.2±11.1 and n-RS: 23.1±6.3; ANOVA, p