Dataset Information

Proteomic analysis identifies novel pathways linking epithelial-to-mesenchymal transition with resistance to HER2-targeted therapy

ABSTRACT: Resistance to Human Epidermal Growth Factor Receptor (HER)-targeted cancer therapies appear to be occurring via common pathways, despite differences in their mechanism of action. This suggests that combination therapies targeting alternative pathways will be needed to overcome resistance. We have used a global proteomics approach to identify common signaling nodes that are required for driving HER2-independent resistance mechanisms to the pan-HER family kinase inhibitors AZD8931 and lapatinib. A novel set of epithelial–to-mesenchymal transition (EMT) associated proteins linked to resistance to pan-HER family targeted therapy was identified. We demonstrate that a sub-set of these genes are predictive of prognosis within the ERBB2 subtype of breast cancers and are worthy of further study in the context of preventing resistance to anti-HER family agents. Furthermore, targeting these pathways, perhaps via combination with galectin-1 or Axl inhibitors may provide additional strategies for the treatment of resistant tumours.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Thierry Le Bihan