Strategies for MMP inhibition in cancer: innovations for the post-trial era.
For more than two decades, the view that tumour-associated matrix metalloproteinases (MMPs) were required for peritumour tissue degradation and metastasis dominated the drive to develop MMP inhibitors as anticancer therapeutics. Until recently, clinical trials with MMP inhibitors have yielded disappointing results, highlighting the need for better insight into the mechanisms by which this growing family of multifunctional enzymes contribute to tumour growth. It is now recognized that MMP activity is tightly regulated at several levels, providing new avenues for blocking these enzymes. What are the different approaches that can be used to target MMPs, and which of these might lead to new therapeutic strategies for cancer?
Overall
Christopher Mark
CM
Department of Oral Biological and Medical Sciences, C.I.H.R. Group in Matrix Dynamics, University of British Columbia, V6T 1Z3, Canada.
López-Otín
Carlos
C
D000818:Animals; D001665:Binding Sites; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases