Spek C Arnold, Versteeg Henri H, Borensztajn Keren S
C. Arnold Spek, H2-157, Academic Medical Center, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands, Tel.: +31 20 5668750, E-mail:
Thromb Haemost. 2015 Aug 31;114(3):530-6. doi: 10.1160/TH15-02-0124. Epub 2015 May 21.
Already since the early 1800s, it has been recognised that malignancies may provoke thromboembolic complications, and indeed cancer patients are at increased risk of developing venous thrombosis. Interestingly, case control studies of deep-vein thrombosis suggested that low-molecular-weight heparin (LMWH) improved survival of cancer patients. This led to the hypothesis that cancer cells might 'take advantage' of a hypercoagulable state to more efficiently metastasise. Initial randomised placebo control trials showed that LMWH improve overall survival of cancer patients, especially in those patients with a relatively good prognosis. The failure of recent phase III trials, however, tempers enthusiasm for anticoagulant treatment in cancer patients despite an overwhelming body of literature showing beneficial effects of anticoagulants in preclinical models. Instead of discarding LMWH as potential (co)treatment modality in cancer patients, these disappointing recent trials should guide future preclinical research on anticoagulants in cancer biology. Most and for all, the underlying mechanisms by which coagulation drives tumour progression need to be elucidated. This could ultimately allow selection of cancer patients most likely to benefit from anticoagulant treatment and/or from targeted therapy downstream of coagulation factor signalling.
自19世纪初以来，人们就已经认识到恶性肿瘤可能引发血栓栓塞并发症，事实上，癌症患者发生静脉血栓形成的风险增加。有趣的是，深静脉血栓形成的病例对照研究表明，低分子量肝素（LMWH）可提高癌症患者的生存率。这导致了一种假设，即癌细胞可能“利用”高凝状态更有效地转移。最初的随机安慰剂对照试验表明，LMWH可提高癌症患者的总体生存率，尤其是那些预后相对较好的患者。然而，尽管大量文献表明抗凝剂在临床前模型中有有益作用，但最近的III期试验失败，使人们对癌症患者抗凝治疗的热情有所降温。这些近期令人失望的试验不应摒弃LMWH作为癌症患者潜在的（联合）治疗方式，而应指导未来关于抗凝剂在癌症生物学中作用的临床前研究。最重要的是，需要阐明凝血驱动肿瘤进展的潜在机制。这最终可能有助于选择最有可能从抗凝治疗和/或凝血因子信号下游的靶向治疗中获益的癌症患者。
