Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy.
The matrix metalloproteinases (MMPs) mediate homeostasis of the extracellular environment. They have multiple signalling activities that are commonly altered during tumorigenesis and that might serve as intervention points for anticancer drugs. However, there are many criteria to consider in validating MMPs as drug targets and for the development of MMP inhibitors. The inhibition of some MMPs could have pro-tumorigenic effects (making them anti-targets), counterbalancing the benefits of target inhibition. These effects might partially account for the failure of MMP inhibitors in clinical trials. What are the major challenges in MMP target validation and MMP-inhibitor-drug development?
University of British Columbia Centre for Blood Research, CBCRA Program in Breast Cancer Metastasis, Department of Oral Biological & Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3. chris.overall@ubc.ca
Christopher M
CM
Overall
Oded
O
Kleifeld
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002471:Cell Transformation, Neoplastic; D005109:Extracellular Matrix / Q000378:metabolism; D005544:Forecasting; D015971:Gene Expression Regulation, Enzymologic; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000145:classification / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D009389:Neovascularization, Pathologic; D011480:Protease Inhibitors / Q000627:therapeutic use*; D019714:Tissue Inhibitor of Metalloproteinases / Q000627:therapeutic use
D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases