Role of matrix metalloproteinases and their inhibitors in pancreatic cancer.
OBJECTIVE
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.
Evans
J D
JD
Department of Surgery, University of Liverpool, Royal Liverpool University Hospital, UK.
Ghaneh
P
P
Kawesha
A
A
Neoptolemos
J P
JP
D002986:Clinical Trials as Topic; D005109:Extracellular Matrix / Q000201:enzymology*; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000145:classification / Q000502:physiology*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000556:secondary; D011480:Protease Inhibitors / Q000494:pharmacology*
D011480:Protease Inhibitors; D008666:Metalloendopeptidases