title: Anticoagulants versus cancer.
abstract: Venous thromboembolism (VTE) and cancer are strongly associated, and present a major challenge in cancer patient treatment. Cancer patients have a higher risk of developing VTE, although the risk differs widely between tumour types. VTE prophylaxis is routinely given to cancer patients, in the form of vitamin K antagonists (VKA) or low molecular weight heparin (LMWH). Several studies have reported that cancer patients receiving anticoagulants show prolonged survival and this effect was more pronounced in patients with a good prognosis, although the mechanism is poorly understood. Tissue Factor (TF) is the initiator of extrinsic coagulation, but its non-haemostatic signalling via protease-activated receptors (PARs) is a potent driver of tumour angiogenesis. Furthermore, coagulation activation is strongly implicated in tumour cell migration and metastasis. This review discusses the effects of anticoagulants on cancer progression in patients, tumour cell behaviour, angiogenesis, and metastasis in in vitro and in vivo models. Inhibition of TF signalling shows great promise in curbing angiogenesis and in vivo tumour growth, but whether this translates to patients is not yet known. Furthermore, non-haemostatic properties of coagulation factors in cancer progression are discussed, which provide exciting opportunities on limiting oncologic processes without affecting blood coagulation.
authors.affiliation: Einthoven Laboratory for Experimental Vascular Medicine, Department of Internal Medicine, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Chris
authors.initials: C
authors.lastname: Tieken
authors.affiliation: Einthoven Laboratory for Experimental Vascular Medicine, Department of Internal Medicine, Leiden University Medical Centre, Leiden, The Netherlands. Electronic address: h.h.versteeg@lumc.nl.
authors.forename: Henri H
authors.initials: HH
authors.lastname: Versteeg
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D003374:Coumarins / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control*; D009369:Neoplasms / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D013925:Thromboplastin / Q000378:metabolism; D054556:Venous Thromboembolism / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D000925:Anticoagulants; D003374:Coumarins; D006495:Heparin, Low-Molecular-Weight; D014812:Vitamin K; D013925:Thromboplastin
keywords: Cancer progression; Coagulation; Coumarins; Low Molecular Weight Heparin; Signal Transduction; Tissue Factor