Potential for metalloproteinase inhibitors in cancer therapy

Abstract

Several potential antineoplastic drugs now in clinical trials seek to defeat cancer by preventing tumours from using matrix metalloproteinase enzymes (MMPs). These enzymes degrade matrix protein substrates such as collagen, laminin, fibronectin and elastin. Consequently, a strategy of inhibiting MMP activity could reduce local tumour invasion and tumour cell migration at either primary or metastatic tumour sites. However, there appears to be a trade off in developing effective MMP inhibitors, delegates were told at the 10th NCI-EORTC Symposium on New Drugs in Cancer Therapy [ Amsterdam, The Netherlands; June 1998 ]. One dilemma is balancing the need to inhibit a spectrum of MMP targets against the potential for adverse effects. In addition, the standard clinical response criteria of ‘tumour shrinkage’, used in clinical trials of antineoplastic agents, may be inadequate for these cytostatic agents.