Matrix Metalloproteinase Inhibitors and Cancer—Trials and Tribulations
Lisa M. Coussens,1
Barbara Fingleton,2
Lynn M. Matrisian2*
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.
1 Department of Pathology and Cancer Research
Institute, University of California, 2340 Sutter Street, San Francisco,
CA 94143, USA.
2 Department of Cancer Biology,
Vanderbilt University, Nashville, TN 37232, USA.
*
To whom correspondence should be addressed. E-mail:
lynn.matrisian{at}vanderbilt.edu
