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Matrix Metalloproteinase Inhibitors and Cancer: Trials and Tribulations
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Matrix Metalloproteinase Inhibitors and Cancer: Trials and Tribulations
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Journal Article
Matrix Metalloproteinase Inhibitors and Cancer: Trials and Tribulations
2002
Overview
For at least 30 years, matrix metalloproteinases (MMPs) have been heralded as promising targets for cancer therapy on the basis of their massive up-regulation in malignant tissues and their unique ability to degrade all components of the extracellular matrix. Preclinical studies testing the efficacy of MMP suppression in tumor models were so compelling that synthetic metalloproteinase inhibitors (MPIs) were rapidly developed and routed into human clinical trials. The results of these trials have been disappointing. Here we review the studies that brought MPIs into clinical testing and discuss the design and outcome of the trials in light of new information about the cellular source, substrates, and mode of action of MMPs at different stages of tumor progression. The important lessons learned from the MPI experience may be of great value for future studies of MPIs and for cancer drug development in general.
Publisher
American Society for the Advancement of Science,American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Animals
/ Antineoplastic Agents - administration & dosage
/ Antineoplastic Agents - pharmacology
/ Antineoplastic Agents - therapeutic use
/ Biological and medical sciences
/ Cancer
/ Dosage
/ Drug Evaluation, Preclinical
/ Enzymes
/ Extracellular Matrix - metabolism
/ Growth
/ Humans
/ Matrix Metalloproteinase Inhibitors
/ Matrix Metalloproteinases - metabolism
/ Pharmacology. Drug treatments
/ Placebos
/ Protease Inhibitors - administration & dosage
/ Protease Inhibitors - pharmacology
/ Protease Inhibitors - therapeutic use
/ Review
/ Tumors
