Targeting of extracellular proteases required for the progression of pancreatic cancer.
BACKGROUND
Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer-related death in the United States. Its lethality is due, in large part, to its resistance to traditional chemotherapeutics. As a result, there is an enormous effort being put into basic research to identify proteins that are required for PDA progression so that they may be specifically targeted for therapy.


OBJECTIVE
To compile and analyze the evidence that suggests that extracellular proteases are significant contributors to PDA progression.


METHODS
We focus on three different extracellular protease subclasses expressed in PDA: metalloproteases, serine proteases and cathepsins. Based on data from PDA and other cancers, we suggest their probable roles in PDA.


CONCLUSIONS
Of the proteases expressed in PDA, many appear to have overlapping functions, based on the substrates they process, making therapeutics complicated. Two protease families most likely to have unique, critical functions during tumor progression, and therefore strong potential as therapeutic targets, are the a disintegrin and metalloproteases (ADAMs) and the cathepsins.
Ardito
Christine M
CM
Stony Brook University, Department of Pharmacological Sciences, BST 8-140, Stony Brook, NY 11794-8651, USA.
Briggs
Courtney D
CD
Crawford
Howard C
HC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy*; D002403:Cathepsins / Q000187:drug effects / Q000378:metabolism; D018849:Controlled Clinical Trials as Topic; D018450:Disease Progression; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D006801:Humans; D045726:Metalloproteases / Q000187:drug effects / Q000378:metabolism; D012697:Serine Endopeptidases / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D002403:Cathepsins; D045726:Metalloproteases; D012697:Serine Endopeptidases