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

Kenny PA

Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS977-225A, University of California, Berkeley, CA 94720, USA. pakenny@lbl.gov

TNF-alpha 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-alpha 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.

Published 2 October 2007 in Expert Opin Ther Targets, 11(10): 1287-98.
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