Between 1970 and 1994, cancer claimed the lives of about 0.5 million Americans every year. According to the most recent statistics, it is estimated that well over 1 million new cases of cancer will be diagnosed and 555,500 people will die from cancer in the United States in the year 2002. From 1992 to 1998, the incidence of cancer related death was reduced by 1.1%. This modest improvement was related to improved detection and greater therapeutic options which can be sub-divided into a number of different therapeutic classes including classic alkylating agents and anti-metabolites and new concepts such as angiogenesis inhibitors and apoptosis activators. A further class that deserves greater attention centers around he mast as is, the balance between thrombosis and clot removal. This balance is an essential component of host defense it's disturbance underlies a large number of diseases, notably cardiovascular diseases such as stroke myocardial infarction and pulmonary embolism and also sepsis which is associated with disseminated intravascular coagulability. Thrombus formation results from the activation of the coagulation pathway culminating in the conversion of fibrinogen to fibrin and the adhesion of platelets. Clot removal involves the breakdown of fibrin following the activation of plasminogen to produce plasmin. In the tumor environment the formation of clots can produce multiple problems. For example, as with septic shock, disseminated intravascular coagulopathy is also very common in cancer patients and indeed, thromboembolism is one of the most common causes of death in this cohort. As well as contributing to the end stages of tumor progression, components of the hemostatic pathways support metastasis and angiogenesis. Plasminogen activation which occurs as a natural response to clot formation may have a direct effect on tumor cells and may also disrupt the tumor cell-extracellular matrix interaction promoting metastasis. On the other hand, Italian researchers have been investigating the effects of thrombin on tumor progression. Human alpha-thrombin which is deposited during clot formation is a growth factor for a variety of cell types, including monocytes and endothelial cells, involved in the control of angiogenesis. In particular, IL-1 and IL-6 expression has been shown to be enhanced by thrombin. This effect was suggested to be mediated through activation of PAR-1, a receptor for thrombin which has been identified as a target for cardiovascular disease. This data suggests that PAR-1 may also be of importance in the treatment of malignancy. This data also adds to the growing body of data supporting the concept that coagulation in the tumor environment may contribute to tumor growth, angiogenesis and metastasis, and as such key components of hemastasis deserve greater attention as candidate anti-cancer treatments.

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