Administration of low molecular weight heparins for prolonging the survival of patients with cancer

Thromboembolism represents one of the most common causes of mortality and morbidity in cancer patients, and thromboembolic events occur more often in patients with biologically more aggressive malignant disease. Therefore, low molecular weight heparins (LMWHs) are routinely administered to cancer patients. Importantly, in addition to the prophylactic activity against thromboembolism, LMWHs seem to decrease mortality in these patients. Improved clinical prognosis is independent of the antithrombotic efficacy, since vitamin K antagonists do not improve patient survival, and non-anticoagulant heparins exhibit a similar anti-cancer effect. This protective effect is primarily related to the prevention of spreading of the cancer through metastases. The mechanisms responsible for heparin-dependent inhibition of metastases comprise: inhibition of integrins, restraint of P- and L-selectin-mediated interactions of the platelets with circulating neoplastic cells, silencing of the chemokine CXCL12/CXCR4 axis, inhibition of heparanase activity, inhibition of neoangiogenesis within the tumour, and reduced local generation of thrombin. A combined effect of the above-described mechanisms is also possible. Although at the moment cancer patients are not recommended routine administration of LMWHs for survival improvement, such a recommendation might be expected in the future. It is possible that for this purpose, instead of currently available agents, some novel heparins or similarly structured chemical compounds will be used.