Cancer treatment with inhibitors of urokinase-type plasminogen activator and plasmin

The urokinase-type plasminogen activator-plasmin system plays an important role in many normal physiological processes including clot lysis, wound healing, embryogenesis and tissue remodelling. It is also involved in the pathogenesis of human malignancy through its ability to mediate tumour cell growth, invasion and metastatic dissemination. Interfering with this system is an appealing approach for experimental therapy of malignancy for several reasons. This concept is supported by a wealth of preclinical data. Evidence exists suggesting a role for this system in several major human tumour types. Preliminary evidence suggests that agents which block this pathway are effective in therapeutic doses that are already defined and relatively non-toxic. This form of treatment is not likely to carry cross-resistance with other types of cancer therapy and should be applicable to both localised and advanced tumours. Since heterogeneity in responsiveness among various tumour types is expected, clinical effects in given tumours would provide a basis for interpreting mechanisms of tumour progression in vivo and for future development of drugs with improved efficacy. Inhibition of the urokinase-type plasminogen activator-plasmin system remains a promising, but largely untested, area of experimental cancer therapeutics.