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Published on: June 13, 2014
Matrix metalloproteinase inhibition: a review of anti-tumour activity
1British Biotech Pharmaceuticals Ltd., Oxford, U.K.
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 metalloproteinases 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.
Insights
Matrix metalloproteinase inhibitors (MMPIs) show promise in halting tumor growth and spread by preventing extracellular matrix degradation and inhibiting angiogenesis. This non-cytotoxic approach may complement existing cancer therapies for metastatic disease.
Area of Science:
- Biochemistry
- Oncology
- Pharmacology
Background:
- Matrix metalloproteinases (MMPs) are enzymes that degrade extracellular matrix components.
- Tumors utilize MMPs to invade and metastasize, overcoming natural barriers.
- MMPs are potential therapeutic targets for treating metastatic cancer.
Purpose of the Study:
- To review the activity of matrix metalloproteinase inhibitors (MMPIs).
- To evaluate MMPIs in experimental tumor models and clinical studies.
Main Methods:
- In vitro studies assessing MMPIs' effect on extracellular matrix degradation.
- In vivo studies using rodent and human xenograft tumor models.
- Phase I/II clinical trials of MMPIs.
Main Results:
- MMPIs inhibit extracellular matrix degradation by tumor cells without being cytotoxic.
- MMPI treatment reduced tumor growth and metastatic spread in experimental models.
- MMPIs demonstrated anti-angiogenic properties, crucial for malignancy progression.
Conclusions:
- MMPI therapy can potentially arrest tumor growth and metastasis.
- As a non-cytotoxic 'tumourostatic' strategy, MMPIs may complement conventional treatments.
- MMPIs offer a promising approach for long-term management of metastatic disease.
