PROTEASE INHIBITORS - ROLE AND POTENTIAL THERAPEUTIC USE IN HUMAN CANCER

Proteases and protease inhibitors have been increasingly recognised as important factors in the physiopathology of human diseases, and our u nderstanding of their role in cancer has dramatically increased over t he last decade. We have obtained causal evidence linking proteases to tumour Invasion and metastasis, and have become aware of genuine mecha nisms used by tumour sells to optimise the use of proteases in the per icellular matrix. Many synthetic and natural inhibitors of these prote ases have also been characterised, and their mechanisms of interaction with their corresponding enzymes are progressively unveiled as the X- ray crystal structures of these enzymes and their inhibitors are now r eported. It has also become evident that many of these inhibitors, in addition to preventing the dissemination of cancer cells, have an inhi bitory effect on tumour growth. Thus protease inhibitors are emerging as potentially therapeutic tools to treat cancer. In this article, rec ent studies on the role of proteases and their inhibitors in cancer ar e reviewed, and current ideas on their potential use as therapeutic ag ents are discussed.