Matrix metalloproteinase inhibition: A review of anti-tumour activity

P. D. Brown, R. Giavazzi

Research output: Contribution to journalArticle

217 Citations (Scopus)

Abstract

Background: Matrix metalloproteinases are a homologous family of proteolytic enzymes. Collectively, these proteinases are capable of degrading all components of the extracellular matrix, including proteolytically resistant fibrillar collagens. Extracellular matrices constitute the principal barrier to tumour growth and spread, and there is now experimental evidence that malignant tumours utilise matrix metalloproteinases to overcome this barrier. Inhibitors of matrix metalloproteinases may therefore be of therapeutic value in the treatment of metastatic disease. Design: This review describes the activity of matrix metalloproteinase inhibitors (MMPIs), in experimental tumour models and in phase I/II clinical studies. Results: Studies with MMPIs in vitro have shown that these agents are not cytotoxic but can inhibit the degradation of extracellular matrix by tumour cells. In experimental tumour models in vivo, MMPI treatment caused inhibition of tumour growth and metastatic spread in both rodent syngeneic and human xenograft models. MMPIs have also been shown to inhibit angiogenesis, a process essential for the rapid growth of most malignancies. Conclusions: MMPI therapy has the potential to arrest tumour growth and spread. As a non-cytotoxic 'tumourostatic' approach it may offer an ideal complement to surgery, radiotherapy and chemotherapy in the successful long-term treatment of metastatic disease.

Original languageEnglish
Pages (from-to)967-974
Number of pages8
JournalAnnals of Oncology
Volume6
Issue number10
Publication statusPublished - 1995

Fingerprint

Matrix Metalloproteinases
Matrix Metalloproteinase Inhibitors
Tumors
Tumor
Inhibitor
Neoplasms
Extracellular Matrix
Tumor Growth
Growth
Peptide Hydrolases
Theoretical Models
Fibrillar Collagens
Therapeutics
Chemotherapy
Review
Metalloproteases
Cytotoxins
Radiotherapy
Heterografts
Collagen

Keywords

  • Cancer therapy
  • Matrix metalloproteinases
  • Metastasis
  • Timp

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Neuropsychology and Physiological Psychology
  • Hematology

Cite this

Matrix metalloproteinase inhibition : A review of anti-tumour activity. / Brown, P. D.; Giavazzi, R.

In: Annals of Oncology, Vol. 6, No. 10, 1995, p. 967-974.

Research output: Contribution to journalArticle

@article{3de13fc0229a489986edfcf98b904434,
title = "Matrix metalloproteinase inhibition: A review of anti-tumour activity",
abstract = "Background: Matrix metalloproteinases are a homologous family of proteolytic enzymes. Collectively, these proteinases are capable of degrading all components of the extracellular matrix, including proteolytically resistant fibrillar collagens. Extracellular matrices constitute the principal barrier to tumour growth and spread, and there is now experimental evidence that malignant tumours utilise matrix metalloproteinases to overcome this barrier. Inhibitors of matrix metalloproteinases may therefore be of therapeutic value in the treatment of metastatic disease. Design: This review describes the activity of matrix metalloproteinase inhibitors (MMPIs), in experimental tumour models and in phase I/II clinical studies. Results: Studies with MMPIs in vitro have shown that these agents are not cytotoxic but can inhibit the degradation of extracellular matrix by tumour cells. In experimental tumour models in vivo, MMPI treatment caused inhibition of tumour growth and metastatic spread in both rodent syngeneic and human xenograft models. MMPIs have also been shown to inhibit angiogenesis, a process essential for the rapid growth of most malignancies. Conclusions: MMPI therapy has the potential to arrest tumour growth and spread. As a non-cytotoxic 'tumourostatic' approach it may offer an ideal complement to surgery, radiotherapy and chemotherapy in the successful long-term treatment of metastatic disease.",
keywords = "Cancer therapy, Matrix metalloproteinases, Metastasis, Timp",
author = "Brown, {P. D.} and R. Giavazzi",
year = "1995",
language = "English",
volume = "6",
pages = "967--974",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "NLM (Medline)",
number = "10",

}

TY - JOUR

T1 - Matrix metalloproteinase inhibition

T2 - A review of anti-tumour activity

AU - Brown, P. D.

AU - Giavazzi, R.

PY - 1995

Y1 - 1995

N2 - Background: Matrix metalloproteinases are a homologous family of proteolytic enzymes. Collectively, these proteinases are capable of degrading all components of the extracellular matrix, including proteolytically resistant fibrillar collagens. Extracellular matrices constitute the principal barrier to tumour growth and spread, and there is now experimental evidence that malignant tumours utilise matrix metalloproteinases to overcome this barrier. Inhibitors of matrix metalloproteinases may therefore be of therapeutic value in the treatment of metastatic disease. Design: This review describes the activity of matrix metalloproteinase inhibitors (MMPIs), in experimental tumour models and in phase I/II clinical studies. Results: Studies with MMPIs in vitro have shown that these agents are not cytotoxic but can inhibit the degradation of extracellular matrix by tumour cells. In experimental tumour models in vivo, MMPI treatment caused inhibition of tumour growth and metastatic spread in both rodent syngeneic and human xenograft models. MMPIs have also been shown to inhibit angiogenesis, a process essential for the rapid growth of most malignancies. Conclusions: MMPI therapy has the potential to arrest tumour growth and spread. As a non-cytotoxic 'tumourostatic' approach it may offer an ideal complement to surgery, radiotherapy and chemotherapy in the successful long-term treatment of metastatic disease.

AB - Background: Matrix metalloproteinases are a homologous family of proteolytic enzymes. Collectively, these proteinases are capable of degrading all components of the extracellular matrix, including proteolytically resistant fibrillar collagens. Extracellular matrices constitute the principal barrier to tumour growth and spread, and there is now experimental evidence that malignant tumours utilise matrix metalloproteinases to overcome this barrier. Inhibitors of matrix metalloproteinases may therefore be of therapeutic value in the treatment of metastatic disease. Design: This review describes the activity of matrix metalloproteinase inhibitors (MMPIs), in experimental tumour models and in phase I/II clinical studies. Results: Studies with MMPIs in vitro have shown that these agents are not cytotoxic but can inhibit the degradation of extracellular matrix by tumour cells. In experimental tumour models in vivo, MMPI treatment caused inhibition of tumour growth and metastatic spread in both rodent syngeneic and human xenograft models. MMPIs have also been shown to inhibit angiogenesis, a process essential for the rapid growth of most malignancies. Conclusions: MMPI therapy has the potential to arrest tumour growth and spread. As a non-cytotoxic 'tumourostatic' approach it may offer an ideal complement to surgery, radiotherapy and chemotherapy in the successful long-term treatment of metastatic disease.

KW - Cancer therapy

KW - Matrix metalloproteinases

KW - Metastasis

KW - Timp

UR - http://www.scopus.com/inward/record.url?scp=0029586589&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029586589&partnerID=8YFLogxK

M3 - Article

C2 - 8750146

AN - SCOPUS:0029586589

VL - 6

SP - 967

EP - 974

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 10

ER -