The blood clotting enzyme, thrombin, is known to stimulate cancer cell invasion by digesting and activating a cell surface tumor ‘switch’ receptor named PAR1. PAR1 is known to be increased in prostate cancer, leading to reduced patient survival. Although thrombin inhibitors have been used with limited success to treat cancer, we propose that a combined approach that blocks both thrombin and its target receptor PAR1 will succeed in stopping prostate cancer cell spread. We will test this idea by using thrombin and PAR inhibitors alone and in combination on human cell lines derived from castrate resistant prostate metastases (PC3 and DU145) and androgen-dependent (LNCaP) prostate cancer in both test-tube and in live animal experiments. In these cells we will also eliminate the production of PAR1 to evaluate their tumor-producing properties without this thrombin target. Our dual approach using both pharmacological blockade as well as genetic deletion will further our understanding of PARs and thrombin action in prostate cancer while potentially enabling a new way to treat this disease.