ROLE OF MATRIX METALLOPROTEINASES AND THEIR INHIBITORS IN PANCREATIC-CANCER

Background/Aims: The matrix metalloproteinases are a family of proteol ytic enzymes which normally have an important physiological role in ti ssue remodelling and wound healing, but more recently have been implic ated in the proteolytic events which occur during tumour invasion. Met hods: The expanding family of matrix metalloproteinases and the specif ic tissue inhibitors of the matrix metalloproteinases are reviewed inc luding their classification, structure, function, regulation of activi ty, and tissue expression with particular reference to pancreatic canc er. The effect of synthetic matrix metalloproteinases inhibitors in pr eclinical studies is reviewed together with the results of ongoing cli nical trials in pancreatic cancer. Results: Pancreatic cancer is assoc iated with the overexpression of several matrix metalloproteinases wit h a reduced expression of their specific inhibitors. Orally bioavailab le matrix metalloproteinase inhibitors have successfully completed pha se I/II clinical trials with promising results. Multicentre randomised controlled phase IIb/III clinical trials area currently under way in pancreatic cancer. Conclusions: Matrix metalloproteinase inhibition ma y represent a novel approach to the management of pancreatic cancer no t only in advanced disease, but in the adjuvant treatment setting foll owing tumour resection either alone or in combination with existing ch emotherapeutic agents.