Stromal degradation by the malignant epithelium in pancreatic cancer and the therapeutic potential of proteolytic inhibition

Abstract:

The matrix metalloproteinases (MMPs) and the tissue inhibitors of the metalloproteinases (TIMPs) are described and reviewed. The role of the MMPs and their inhibitors in tumour invasion and metastasis is reviewed and the interaction between the extracellular matrix and these enzymes is discussed. The expression and activity of the MMPs and TIMPs in pancreatic cancer is reported with reference to the literature and the author's own work. The effect of MMP inhibitors (MMPIs) in vivo and the use of batimastat and marimastat (both; British Biotech Pharmaceuticals, Oxford, UK) in animal experiments are also described. Preliminary phase II and III clinical trial data of marimastat in advanced pancreatic cancer is reported.