Heparin and Cancer

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Abstract
Heparin has been the subject of intensive investigation for decades by both basic and clinical scientists because of its usefulness as a therapeutic anticoagulant (1). In addition to its effects on coagulation, however, heparin exhibits many other activities which seem to have little to do with anticoagulation (2). Goerner first observed an effect on the natural history of malignancy in 1930 when he demonstrated that heparin inhibited tumor growth in experimental animals (3). A substantial body of literature on heparin and cancer has developed during the ensuing decades. A recent increase in interest has resulted from observations made during prospective, randomized clinical trials which compared unfractionated heparin (UH) with low molecular weight heparin (LMWH) for the prevention and treatment of venous thromboembolism (VTE). Several studies have shown improvement in short to intermediate term survival in the subset of patients with cancer who received LMWH. This improved outcome has been emphasized in two published meta-analyses (4, 5), and the trend is supported by the results of a more recent prospective study (6). The improved cancer outcome could not be attributed to prevention of VTE in any of the studies; therefore, it is reasonable to hypothesize that a beneficial effect of heparin may be mediated by mechanisms independent of anticoagulation. Heparin has several properties that may plausibly explain its effect on experimental and human malignancy. The purpose of this paper is to summarize the literature on heparin and cancer and review mechanisms by which heparin may exert antineoplastic activity. The goal is to encourage both definitive clinical trials of heparin on cancer outcome and further studies of drug mechanisms in human malignancy. LMWH, with its favorable pharmacokinetic attributes, is suitable for chronic outpatient administration and is an excellent candidate for further investigation. Such a departure from conventional experimental cytotoxic chemotherapy holds promise for development of novel forms of growth regulatory therapy that interrupt pathways of cancer progression. In this review, “heparin” will refer to unfractionated heparin (UH), and “UH” and “LMWH” will be used to distinguish between the two molecular forms.