Matrix metalloproteinase inhibitors.

Matrix metalloproteinases (MMPs) are a family of enzymes responsible for the breakdown of proteins of connective tissue. Through this action they play an important role in growth, development and tissue repair. Recent studies also suggest that MMPs are utilised in cancer, facilitating both local tumour invasion and metastasis. Levels of certain MMPs such as stromelysin-3 and gelatinase are elevated in tumour-associated stroma compared to non-involved tissue. A series of synthetic low molecular weight MMP inhibitors have been produced. Early inhibitors were based on the peptide structure of collagen, although more recently non-peptide inhibitors have also been developed. The inhibitors are selective for the MMP family and are active at low nanomolar concentrations. Experiments in models of breast cancer have shown that MMP inhibitors can significantly reduce the growth rate of both primary and secondary tumours, and can block the process of metastasis. Several MMP inhibitors have now started clinical trials in patients with advanced malignancy. Although not the optimum setting for a tumouristatic agent, early results suggest this approach may be effective in slowing tumour growth. Trials in the adjuvant setting will provide the most important test of these inhibitors and should determine their potential to complement existing cytoreductive treatments and prolong survival.