Matrix metalloproteinase inhibitors as anticancer agents.
The important role of matrix metalloproteinases (MMPs) in the process of carcinogenesis is well established. However, despite very promising activity in a plethora of preclinical models, MMP inhibitors (MMPIs) failed to demonstrate a statistically significant survival advantage in advanced stage clinical trials in most human malignancies. Herein, we review the implication of MMPs in carcinogenesis, outline the pharmacology and current status of various MMPIs as anticancer agents and discuss the etiologies for the discrepancy between their preclinical and clinical evaluation. Finally, strategies for effective incorporation of MMPIs in current anticancer therapies are proposed.
Konstantinopoulos
Panagiotis A
PA
Department of Biological Chemistry, Medical School, University of Athens, 11527 Athens, Greece.
Karamouzis
Michalis V
MV
Papatsoris
Athanasios G
AG
Papavassiliou
Athanasios G
AG
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005544:Forecasting; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy*; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011480:Protease Inhibitors / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011480:Protease Inhibitors; D008666:Metalloendopeptidases