Are proteinase inhibitors potentially useful in tumor therapy?

Within the last 15 years a vast literature has arisen, which associates increased levels of proteinase activity with most in vitro transformed malignant cells and many tumor cells in vivo. As a consequence, proteinase inhibitors have been widely proposed as potential candidates for therapeutic use. The present review shows that in some studies proteinase inhibitors produced significant anti-tumor effects, while in most other studies only limited effects or no effects were observed. In some instances, opposite, or tumor enhancing, effects by proteinase inhibitors were observed. The reasons for the lack of a clear-cut success of proteinase inhibitors in tumor therapy may be: (1) proteinases may not be crucially involved in tumor growth and spread; (2) proteinases which may be crucially involved have not yet been identified; (3) lack of potent inhibitors with appropriate specificity, or use of inappropriate inhibitors or regimens.