Treatment of cancer with anticoagulants: rationale in the treatment of melanoma.

The blood coagulation mechanism regulates the growth and dissemination of malignancy by multiple mechanisms, and anticoagulant drugs have been shown to inhibit the progression of certain cancers. Although progress has been slow, there is ample information on the effects of anticoagulants in various tumors that suggests that the use of anticoagulants has considerable potential in the treatment of some cancers. For example, melanoma is one of a small number of human tumor types in which the tumor is associated with an intact coagulation pathway leading to thrombin generation and conversion of fibrinogen to fibrin in situ immediately adjacent to viable tumor cells. Observations in experimental models combined with the limited clinical trial data on this subject suggest that inhibition of tumor cell thrombin generation may improve outcomes in melanoma cases. Thus, we postulate that pharmacological interruption of the tumor cell-associated coagulation pathway at any one step or even at multiple levels might constitute effective therapy for this disease. Drugs that block the activity of tissue factor, factor Xa, or thrombin are available for clinical testing and, if effective, offer the prospect of a relatively nontoxic, novel treatment for this aggressive tumor.