Rickles Frederick R
Departments of Medicine, Pediatrics and Pharmacology and Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA.
Thromb Res. 2009;123 Suppl 2:S16-20. doi: 10.1016/S0049-3848(09)70004-0.
Both women and men with cancer are at increased risk for developing venous thromboembolism (VTE), a propensity that has been known for many years. Until recently it was assumed, however, that the association between cancer and thrombosis is an epiphenomenon - not causally related to the transforming malignant events. The pathophysiology of thrombosis in patients with cancer is complex involving multiple tumor-related and host-related factors. Several recent studies have provided strong evidence that activation of blood coagulation, perhaps most often mediated by tissue factor (TF)-rich microparticles (MPs), is linked directly to oncogene-induced malignant transformation. In addition, the development of VTE, either before or concurrent with the diagnosis of cancer, appears to predict an aggressive behavior of a tumor, and correlates with increased tumor angiogenesis and early onset of distant metastasis. The regulation of expression of TF in tumor cells is 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-factor 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.
患有癌症的女性和男性发生静脉血栓栓塞（VTE）的风险均会增加，这种倾向多年来已为人所知。然而，直到最近人们还认为，癌症与血栓形成之间的关联是一种附带现象——与恶性转化事件没有因果关系。癌症患者血栓形成的病理生理学很复杂，涉及多种肿瘤相关和宿主相关因素。最近的几项研究提供了强有力的证据，表明凝血激活（可能最常见的是由富含组织因子（TF）的微粒（MPs）介导）与癌基因诱导的恶性转化直接相关。此外，在癌症诊断之前或同时发生的VTE的发展似乎预示着肿瘤的侵袭性，并与肿瘤血管生成增加和远处转移的早期发生相关。肿瘤细胞中TF表达的调控在分子水平上受几种癌基因控制，血小板功能的重要调节因子环氧合酶-2（COX-2）和纤维蛋白溶解抑制剂纤溶酶原激活物抑制剂1型（PAI-1）似乎也是如此。此外，现已证明TF-因子VIIa复合物、因子Xa和/或凝血酶对蛋白酶激活受体（PARs）的作用对肿瘤生长、血管生成和转移很重要。因此，针对癌症中的凝血反应可能为癌症治疗提供一种独特的方法。
