Matrix Metalloproteinase Inhibitors and Cancer—Trials and Tribulations

Coussens, Lisa M.; Fingleton, Barbara; Matrisian, Lynn M.

doi:10.1126/science.1067100

Cited by 2,761Protease and Inhibitor MechanismsTGF-β signaling in diseasesPeptidase Inhibition and Analysis

Matrix Metalloproteinase Inhibitors and Cancer—Trials and Tribulations

Coussens, Lisa M., Fingleton, Barbara, Matrisian, Lynn M.·2002·Science

DOI 10.1126/science.1067100

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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.

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Trials with MMP inhibitors have had mixed results, with efficacy reported mostly during early tumour progression.
“Given their diverse actions, it is also not surprising that trials with MMP inhibitors have had mixed results, with efficacy reported mostly during early tumour progression66.”
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Authors: Coussens, L. M., Fingleton, B., & Matrisian, L. M.
Affiliations: University of California, San Francisco (US)
Vanderbilt University (US)
Corresponding author: Matrisian, Lynn M.
ORCID: Coussens, Lisa M.
Fingleton, Barbara
Matrisian, Lynn M.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2002-03-29
Volume: 295
Issue: 5564
Pages: 2387-2392
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1067100
OpenAlex: W1984483611
Cited by: 2,761
References: 48
Citations by year: 2026: 27 · 2025: 42 · 2024: 60 · 2023: 65 · 2022: 78 · 2021: 83 · 2020: 74 · 2019: 116 · 2018: 92 · 2017: 110 · 2016: 118 · 2015: 135 · 2014: 125 · 2013: 135 · 2012: 152
FWCI: 11.60
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (P50-CA90949, R01 CA 84360, P30 CA 68485, CA72006, P01CA072006, R01CA060867, R01CA60867, R01CA084360, P50CA090949, P30CA068485)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
Keywords: matrix metalloproteinases, metalloproteinase inhibitors, cancer therapy, clinical trials, extracellular matrix degradation, tumor progression, anticancer drug development, preclinical to clinical translation
MeSH terms: Animals, Antineoplastic Agents, Clinical Trials as Topic, Drug Evaluation, Preclinical, Extracellular Matrix, Humans, Neoplasm Metastasis, Neoplasms, Protease Inhibitors, Disease Progression, Matrix Metalloproteinases, Matrix Metalloproteinase Inhibitors

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Matrix Metalloproteinase Inhibitors and Cancer—Trials and Tribulations

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