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Speaker Disclosure
Eisai - Speaker's Bureau; consultant
sanofi-aventis - consultant
Bristol Myers Squibb - consultant
Othera - Chief Scientific Officer
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46 slide(s)
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Abstract
Until recently, the well-known increased risk for venous thromboembolism (VTE) in patients with cancer has been considered an epiphenomenon – not causally related to the transforming malignant events. While it remains true that the pathophysiology of thrombosis in cancer is complex with multiple tumor-related and host-related factors involved, recent landmark studies have directly linked activation of blood coagulation with malignant transformation (oncogenesis) at the molecular level. These observations now provide the missing step that explains better the close relationship that has been observed between thrombosis, aggressive behavior of tumors, angiogenesis and metastasis. The regulation of expression of the major activator of mammalian coagulation, tissue factor (TF), has been demonstrated to be controlled at the molecular level by several oncogenes, as appears to be true for cyclooxygenase-2 (COX-2), an important regulator of platelet function and plasminogen activator inhibitor type 1 (PAI-1), an inhibitor of fibrinolysis. In addition, engagement of protease activated receptors (PARs) by the TF-VIIa complex, factor Xa and/or thrombin, have now been shown to be important for tumor growth, angiogenesis and metastasis. Targeting blood clotting reactions in cancer, therefore, may provide a unique approach to cancer treatment.
Learning objectives
1. Pathophysiology of thrombosis in cancer;
2. Role of tissue factor(TF)in tumor cell signaling and angiogenesis through protease-activated receptors (PARs);
3. Molecular regulation of TF, other blood coagulation factors, platelet function and fibrinolysis by tumor oncogenes;
4. Possible utility of TF(and other clotting proteins) as new targets for antineoplastic therapy;
5. Rationale for use of anticoagulants as antineoplastic therapy.
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