ABSTRACT
Patients who present with idiopathic venous thromboembolism (VTE) frequently harbor an occult cancer that does not become clinically evident until months or even years later. Although Professor Armand Trousseau first recognized this link between coagulation and malignancy in 1865,1 the mechanisms underlying this association have only recently started to unravel. The key mediator of this link is tissue factor (TF), the primary initiator of the coagulation cascade. Via both clotting-dependent and clotting-independent pathways, TF induces angiogenesis, the process of generating new blood vessels from pre-existing vessels, a process that is essential for tumor growth and metastasis. Other players downstream of TF activation that also induce angiogenesis include thrombin, protease-activated receptors (PARs), and fibrin, some of which are schematically represented in Figure 6.1. This chapter will dissect the coagulation cascade from TF activation through fibrin deposition, and will explore how key members of this cascade contribute directly and/or indirectly to tumor angiogenesis. While the principal goal of this chapter is to provide evidence supporting the hypothesis that tumor angiogenesis is the central link between blood coagulation and tumorigenesis, tumor growth may be promoted by coagulation products via pathways other than those related to angiogenesis. Fields of experimental oncology and thrombosis are being bridged to develop novel approaches that may hold promise for the treatment of cancer.
