Tackling EGFR signaling with TACE antagonists: a rational target for metalloprotease inhibitors in cancer

TNF-α converting enzyme (TACE/ADAM17) is a transmembrane metalloprotease that plays a key role in the cleavage and mobilization of receptor ligands that are initially synthesized as membrane-tethered precursors. For many years, attention has focused on the role of TACE-dependent TNF-α cleavage in arthritis and, more recently, it has become apparent that TACE also plays an important role in regulating epidermal growth factor receptor activity in several tumor types. This review presents the background to these findings and a rationale for the continued development of TACE inhibitors for the treatment of epidermal growth factor receptor-dependent epithelial tumors.