Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2387-2392 |
| Number of pages | 6 |
| Journal | Science |
| Volume | 295 |
| Issue number | 5564 |
| DOIs | |
| State | Published - Mar 29 2002 |
| Externally published | Yes |
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ASJC Scopus subject areas
- General
Cite this
Matrix metalloproteinase inhibitors and cancer : Trials and tribulations. / Coussens, Lisa; Fingleton, Barbara; Matrisian, Lynn M.
In: Science, Vol. 295, No. 5564, 29.03.2002, p. 2387-2392.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Matrix metalloproteinase inhibitors and cancer
T2 - Trials and tribulations
AU - Coussens, Lisa
AU - Fingleton, Barbara
AU - Matrisian, Lynn M.
PY - 2002/3/29
Y1 - 2002/3/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037192458&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037192458&partnerID=8YFLogxK
U2 - 10.1126/science.1067100
DO - 10.1126/science.1067100
M3 - Article
C2 - 11923519
AN - SCOPUS:0037192458
VL - 295
SP - 2387
EP - 2392
JO - Science
JF - Science
SN - 0036-8075
IS - 5564
ER -