ADAM metalloproteases and EGFR signalling

Epidermal growth factor receptor (EGFR) comprises a dominant signalling pathway for many tumours. In breast cancer, increased expression of EGFR or its EGF-like ligands and hyperactivation of subsequent mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) signalling have been linked to anti-hormone resistant growth, metastatic progression and poor prognosis. Considerable data exist detailing EGFR activation and the downstream signalling that is triggered subsequent to EGFR ligand binding, allowing rationale design of several anti-EGFR agents that are currently in clinical trials in cancers including the breast. However, less is known about the mechanisms regulating EGF-like ligand availability and their potential as therapeutic targets.