Type

Journal Article

Authors

Michael J Duffy
John Crown
Patricia McGowan
Maeve Mullooly

Subjects

Biochemistry

Topics
clinical trials cell proliferation extracellular matrix proteins receptors growth factor cell adhesion cell migration low molecular weight cancer treatment

The ADAMs Family of Proteases as Targets for the Treatment of Cancer. (2016)

Abstract The ADAMs (a disintegrin and metalloproteases) are transmembrane multidomain proteins implicated in multiple biological processes including proteolysis, cell adhesion, cell fusion, cell proliferation and cell migration. Of these varied activities, the best studied is their role in proteolysis. However, of the 22 ADAMs believed to be functional in humans, only approximately a half possess matrix metalloproteinase (MMP)-like protease activity. In contrast to MMPs which are mostly implicated in the degradation of extracellular matrix proteins, the main ADAM substrates are the ectodomains of type I and type II transmembrane proteins. These include growth factor/cytokine precursors, growth factor/cytokine receptors and adhesion proteins. Recently, several different ADAMs, especially ADAM17, have been shown to play a role in the development and progression of multiple cancer types. Consistent with this causative role in cancer, targeting ADAM17 with either low molecular weight inhibitors or monoclonal antibodies was shown to have anti-cancer activity in multiple preclinical systems. Although early phase clinical trials have shown no serious side effects with a dual ADAM10/17 low molecular weight inhibitor, the consequences of long-term treatment with these agents is unknown. Furthermore, efficacy in clinical trials remains to be shown.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Michael J Duffy, John Crown, Patricia McGowan, Maeve Mullooly

Experts in our system

1
Michael J Duffy
University College Dublin
 
2
John Crown
Dublin City University
Total Publications: 104
 
3
Patricia M McGowan
Dublin City University
Total Publications: 8
 
4
Maeve Mullooly
University College Dublin