The pathogenesis of venous thromboembolism in cancer: emerging links with tumour biology.
Venous thromboembolism (VTE) is a frequent complication in individuals with cancer and is considered to be a cause of substantial mortality. Epidemiological studies identify malignancy as an independent VTE risk factor and show that cancer patients are at increased risk of both initial and recurrent VTE events. The risk due to cancer is compounded by the effects of chemotherapy and other treatments. The pathogenesis of cancer-associated VTE is complex involving multiple interactions between tumours and various components of haemostasis. The development of a systemic hypercoagulable state is considered a key pathogenetic feature and is attributed to tumour expression of tissue factor and other procoagulants, activation of vascular cells by tumour-derived cytokines and adhesive interactions between tumour cells and host cells. An increasing body of evidence indicates that the activation of haemostasis in malignant disease contributes to tumour growth and progression by stimulation of intracellular signalling pathways. The interaction of tissue factor, thrombin and other coagulation factors with protease activated receptor (PAR) proteins expressed by tumour cells and host vascular cells leads to the induction of genes related to the processes of angiogenesis, cell survival and cell adhesion and migration.
Winter
Paul C
PC
Department of Haematology, Belfast City Hospital, Belfast, N. Ireland. paul.winter@bll.n-i.nhs.uk
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D013923:Thromboembolism / Q000209:etiology / Q000378:metabolism* / Q000401:mortality; D020246:Venous Thrombosis / Q000209:etiology / Q000378:metabolism* / Q000401:mortality
D000970:Antineoplastic Agents; D001779:Blood Coagulation Factors