MATRIX METALLOPROTEINASE INHIBITORS - A REVIEW

The matrix metalloproteinases (MMPs) are a family of closely related, zinc-dependent proteolytic enzymes. Collectively, they ase capable of degrading all the components of the extracellular matrix and as such a re involved in a number of physiological and pathological processes. T he extracellular matrix is the principal barrier to tumour growth and spread, and there is evidence that MMPs play a role in the processes o f tumour growth and metastasis. Therefore, inhibitors of MMPs may be o f value in the treatment of malignant disease. There exist naturally o ccurring inhibitors of these enzymes known as 'tissue inhibitors of MM Ps', or TIMPs. Although there have been considerable preclinical studi es on these inhibitors, they are as yet unavailable for use as therape utic drugs. Research in this field has focused largely on the developm ent of low molecular weight (<500D) synthetic inhibitors of MMPs. In t his review we focus on the various subgroups of MMP inhibitors now ava ilable, their preclinical evaluation and the limited information avail able from preliminary clinical trials. We comment on the suitability o f the preclinical models used and the difficulty in designing clinical trials of these drugs. We focus on future developments which may invo lve the use of these drugs in combination with existing chemotherapeut ic regimens to achieve a synergistic effect.The matrix metalloproteina ses (MMPs) are a family of closely related zinc-dependent proteolytic enzymes. Collectively, these enzymes an capable of degrading all the c omponents of the extracellular matrix (ECM) [table I]. The ECM is the principal barrier to tumour growth and spread, inhibitors of MMPs may be of therapeutic value in the treatment of malignant disease.([1]).