Hypoxic microenvironment promotesresistance to targeted therapies in HER2-overexpressing breast cancer involving epithelial-to-mesenchymal transition features

WOLOS VJ; TAPIA IJ; ABRIGO M; LACUNZA E; BAL DE KIER JOFFÉ ED; FISZMAN GL

Congreso; AACR Annual Meeting 2021; 2021

Trastuzumab and trastuzumab emtansine (T-DM1) targeted therapies are the main choice for the treatment of HER2-overexpressing breast cancer patients. However, de novo or acquired resistance is still the major obstacle in clinical practice. It has been shown that several pathways, including HER2, can lead to HIF-α stabilization in breast cancer cells. Thus, the purpose of our study was to analyse the effect of hypoxia in acquired resistance to anti-HER2 therapies. We used HER2-overexpressing BT-474 and non-overexpressing MCF-7 human breast cancer cell lines. As an acute hypoxia model, we added CoCl2 (100 µM) to cell culture medium. The hypoxic status of the cells was evaluated by a Western blot analysis, showing a peak of HIF-1α expression after 6 hours of CoCl2 exposure. This result correlated with VEGF induction, as measured by RT-qPCR (p