Abstract
Synthetic serine protease inhibitors, such as nafamostat mesilate, gabexate mesilate and ulinastatin inhibit various kinds of plasma proteinases and are widely used for treatment of pancreatitis, disseminated intravascular coagulation and as an anticoagulant for hemolysis. Several reports describe in preclinical cancer models that synthetic serine protease inhibitors induce apoptosis, prevent tumor invasion or metastasis, and sensitize chemotherapy by inhibiting NF-κB activity, proteinases such as urokinase-type plasminogen activator (u-PA) and matrix metalloproteinases (MMPs) and trypsin combined with protease-activated receptor-2 (PAR-2). Nafamostat mesilate, the first synthetic serine protease inhibitor that underwent clinical testing, has showed impressive anti-tumor effect and manageable toxicities in Phase I and II trials by combination chemotherapy of gemcitabine with nafamostat mesilate for unresectable pancreatic cancer. Synthetic serine protease inhibitors have minimal adverse effects and will have a potential to become a new therapeutic option for cancer patients. Below we discuss the rationale behind targeting the serine protease inhibitor for cancer therapy, and review the preclinical and clinical data.
Published Version
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