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Role of Matrix Metalloproteinases and Their Inhibitors in Pancreatic Cancer

Role of Matrix Metalloproteinases and Their Inhibitors in Pancreatic Cancer Background/Aims: The matrix metalloproteinases are a family of proteolytic enzymes which normally have an important physiological role in tissue remodelling and wound healing, but more recently have been implicated in the proteolytic events which occur during tumour invasion. Methods: The expanding family of matrix metalloproteinases and the specific tissue inhibitors of the matrix metalloproteinases are reviewed including their classification, structure, function, regulation of activity, and tissue expression with particular reference to pancreatic cancer. The effect of synthetic matrix metalloproteinases inhibitors in preclinical studies is reviewed together with the results of ongoing clinical trials in pancreatic cancer. Results: Pancreatic cancer is associated with the overexpression of several matrix metalloproteinases with a reduced expression of their specific inhibitors. Orally bioavailable matrix metalloproteinase inhibitors have successfully completed phase I/II clinical trials with promising results. Multicentre randomised controlled phase IIb/III clinical trials aren currently under way in pancreatic cancer. Conclusions: Matrix metalloproteinase inhibition may represent a novel approach to the management of pancreatic cancer not only in advanced disease, but in the adjuvant treatment setting following tumour resection either alone or in combination with existing chemotherapeutic agents. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Digestion Karger

Role of Matrix Metalloproteinases and Their Inhibitors in Pancreatic Cancer

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Publisher
Karger
Copyright
© 1997 S. Karger AG, Basel
ISSN
0012-2823
eISSN
1421-9867
DOI
10.1159/000201495
Publisher site
See Article on Publisher Site

Abstract

Background/Aims: The matrix metalloproteinases are a family of proteolytic enzymes which normally have an important physiological role in tissue remodelling and wound healing, but more recently have been implicated in the proteolytic events which occur during tumour invasion. Methods: The expanding family of matrix metalloproteinases and the specific tissue inhibitors of the matrix metalloproteinases are reviewed including their classification, structure, function, regulation of activity, and tissue expression with particular reference to pancreatic cancer. The effect of synthetic matrix metalloproteinases inhibitors in preclinical studies is reviewed together with the results of ongoing clinical trials in pancreatic cancer. Results: Pancreatic cancer is associated with the overexpression of several matrix metalloproteinases with a reduced expression of their specific inhibitors. Orally bioavailable matrix metalloproteinase inhibitors have successfully completed phase I/II clinical trials with promising results. Multicentre randomised controlled phase IIb/III clinical trials aren currently under way in pancreatic cancer. Conclusions: Matrix metalloproteinase inhibition may represent a novel approach to the management of pancreatic cancer not only in advanced disease, but in the adjuvant treatment setting following tumour resection either alone or in combination with existing chemotherapeutic agents.

Journal

Digestion – Karger

Published: Jan 1, 1997

Keywords: Batimastat; Pancreatic cancer; Matrix metalloproteinases; Tissue inhibitors, metalloproteinases; Marimastat

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