Angiogenesis and Hemostasis in Hematological Neoplasias

H.      Negaard; A.      Dahm; P.   M.   Sandset; P.   O.   Iversen; B.      Ostenstad

Abstract

Angiogenesis is essential for tumor growth and metastasis. This is firmly established in solid tumors, but accumulating evidence suggests that this is also an important event in hematological neoplasias. Angiogenesis is therefore a putative target for therapy. The potential application of different angiogenesis inhibitors is currently under intense clinical investigation, and we will here review a number of these trials. The association between cancer and thromboembolic disease is even better documented, and again, this is not limited to solid tumors. It appears that many patients with hematological malignancies have a dysfunctional hemostatic system, with increased risk of thromboembolism. Furthermore, effective antithrombotic therapy seems to reduce the risk of cancer progression and even prolongs overall survival. In this review we will thus discuss the mechanisms involved in the regulation of angiogenesis and hemostasis and present evidence for a shared biology. A number of factors regulating the hemostatic system also have pro- or anti-angiogenic properties. Tissue factor (TF) and TF pathway inhibitor (TFPI) seem to play a central role, and there are several lines of evidence suggesting a close cooperation between TF/TFPI and pro-angiogenic factors like members of the vascular endothelial growth factor family. A better understanding of this shared biology may reveal new targets, and will probably increase the safety of targeting the blood supply.

Keywords: angiogenesis, hemostasis, leukemias, lymphomas, tissue factor, tissue factor pathway inhibitor

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