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<dc:creator>Creedon, Helen</dc:creator>
<dc:creator>Gómez Cuadrado, Laura</dc:creator>
<dc:creator>Tarnauskaitė, Žygimantė</dc:creator>
<dc:creator>Balla, Jozef</dc:creator>
<dc:creator>Canel, Marta</dc:creator>
<dc:creator>MacLeod, Kenneth G.</dc:creator>
<dc:creator>Serrels, Bryan</dc:creator>
<dc:creator>Fraser, Craig</dc:creator>
<dc:creator>Unciti-Broceta, Asier</dc:creator>
<dc:creator>Tracey, Natasha</dc:creator>
<dc:creator>Le Bihan, Thierry</dc:creator>
<dc:creator>Kilnowska, Teresa</dc:creator>
<dc:creator>Sims, Andrew H.</dc:creator>
<dc:creator>Byron, Adam</dc:creator>
<dc:creator>Brunton, Valerie G.</dc:creator>
<dc:date>2016-02</dc:date>
<dc:description>Resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapies in the treatment of HER2-positive breast cancer is a major clinical problem. To identify pathways linked to resistance, we generated HER2-positive breast cancer cell lines which are resistant to either lapatinib or AZD8931, two pan-HER family kinase inhibitors. Resistance was HER2 independent and was associated with epithelial-to-mesenchymal transition (EMT), resulting in increased proliferation and migration of the resistant cells. Using a global proteomics approach, we identified a novel set of EMT-associated proteins linked to HER2-independent resistance. We demonstrate that a subset of these EMT-associated genes is predictive of prognosis within the ERBB2 subtype of human breast cancers. Furthermore, targeting the EMT-associated kinases Src and Axl potently inhibited proliferation of the resistant cells, and inhibitors to these kinases may provide additional options for the treatment of HER2-independent resistance in tumors.</dc:description>
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<dc:identifier>http://hdl.handle.net/10259/9792</dc:identifier>
<dc:language>eng</dc:language>
<dc:publisher>Impact Journals</dc:publisher>
<dc:title>Identification of novel pathways linking epithelial-to-mesenchymal transition with resistance to HER2-targeted therapy</dc:title>
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