Title:Targeting ADAM17 Sheddase Activity in Cancer
Volume: 17
Issue: 16
Author(s): Armando Rossello, Elisa Nuti, Silvano Ferrini and Marina Fabbi
Affiliation:
Keywords:
ADAM17, cancer, small molecule inhibitor, antibodies.
Abstract: A disintegrin and metalloprotease (ADAM)17 is a sheddase, capable of releasing
the ectodomains of membrane proteins such as growth factors (e.g. Epidermal
Growth Factor Receptor ligands), cytokines and their receptors, adhesion and signaling
molecules. These activities regulate several physiological and pathological processes
including inflammation, tumor growth and metastatic progression. In this review,
we will summarize ADAM17 biology and focus on its role in cancer and the
possible usage of ADAM17 inhibitors in cancer therapy. Recent achievements in this
area include the development of small molecule metalloprotease inhibitors with enhanced
specificity for ADAM17, monoclonal antibodies, and synthetic short RNA
molecules for gene silencing. These approaches successfully inhibited cancer cell
growth and invasiveness or sensitized them to cytotoxic drugs, ionizing radiations or targeted therapies,
in preclinical studies. These findings suggest the repositioning of ADAM17 inhibitors, which have yet
proven unsuccessful as anti-inflammatory agents, for the development of new anti-cancer therapies, particularly
in EGFR ligand-dependent cancers. Future studies should address ADAM17 inhibitors as
short-term treatments in combination with different anti-cancer therapies.
