Zhang Ning, Lou Weihua, Ji Fang, Qiu Lihua, Tsang Benjamin K, Di Wen
Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China.
Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, China.
J Cancer Res Clin Oncol. 2016 Aug;142(8):1807-16. doi: 10.1007/s00432-016-2131-6. Epub 2016 Feb 24.
The relationship between cancer and thrombosis is complex, as the hemostatic system is inextricably linked to the mechanisms of cancer growth and metastasis. The coagulation system thus appears to be a site for oncogenic events and necessary for the survival and spread of malignant cells. Although several meta-analyses on the effectiveness of unfractionated heparin and low molecular weight heparin (LMWH) in the treatment of venous thromboembolism (VTE) have suggested a lower mortality risk in cancer patients receiving LMWH, this contention has not received general acceptance. In fact, there exist no sufficiently powered studies to date supporting the routine use of LMWH to improve cancer survival. Meanwhile, the molecular mechanism underlying the anti-neoplastic effect of LMWH which is independent of its anti-coagulant function is largely unexplored and is a topic of active investigation.
In this communication, we aimed to review comprehensively evidences from clinical trials, meta-analysis as well as experimental molecular research and to identify future research areas of importance so as to stimulate future research on the potential anti-tumor action of LMWH.
Although benefit of LMWH on cancer patients' survival is controversial depending on the tumor type, cancer stage as well as LMWH type, it appears to be associated with a reduction in VTE and increased bleeding is minor and controllable; thus, randomized controlled trials targeting the survival benefit of certain specific LWMH are needed and justified, and more in-depth experimental researches are imperative to elucidate the anti-tumor effect of anticoagulants.
癌症与血栓形成之间的关系错综复杂,因为止血系统与癌症生长和转移机制紧密相连。凝血系统因此似乎是致癌事件发生的场所,也是恶性细胞存活和扩散所必需的。尽管多项关于普通肝素和低分子量肝素(LMWH)治疗静脉血栓栓塞症(VTE)有效性的荟萃分析表明,接受LMWH治疗的癌症患者死亡风险较低,但这一观点尚未得到普遍认可。事实上,迄今为止尚无足够有力的研究支持常规使用LMWH来提高癌症患者的生存率。与此同时,LMWH独立于其抗凝功能的抗肿瘤作用的分子机制在很大程度上尚未得到探索,是一个正在积极研究的课题。
在本论文中,我们旨在全面回顾来自临床试验、荟萃分析以及实验分子研究的证据,并确定未来重要的研究领域,以激发对LMWH潜在抗肿瘤作用的进一步研究。
尽管LMWH对癌症患者生存的益处因肿瘤类型、癌症分期以及LMWH类型而异,存在争议,但它似乎与VTE的减少相关,且出血增加幅度较小且可控;因此,针对某些特定LMWH生存获益的随机对照试验是必要且合理的,并且必须进行更深入的实验研究以阐明抗凝剂的抗肿瘤作用。