Keywords
Abstract
The review reflects the current state of researches on the antimetastatic activity of direct-acting anticoagulants, in particular, unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs). Antimetastatic effects of such LMWHs as tinzaparin, dalteparin, nadroparin, enoxaparin, reviparin and
bemiparin are considered in detail. A separate section is devoted to the generalization of the mechanisms of antimetastatic effects of these anticoagulants.
The aim of the study is to analyze and generalize literature data on the antimetastatic activity of direct-acting anticoagulants (UFH and LMWH).
The presented experimental data show that UFH and LMWHs prevent metastases, reduce primary tumor growth and increase survival in animal models of metastatic tumors. Clinical data on the use of UFH and LMWHs in patients with oncology, including metastases, turned out to be less weighty. In addition, under the use of UFH and LMWHs in patients with malignant neoplasms, there is a risk of bleeding.
The construction of complex drugs containing a cytostatic agent and LMWH is a promising way to create antimetastatic agents. The most often used model to study an antimetastatic effect of UFH and LMWHs in vitro and in animals was melanoma B16F10. Among the mechanisms of antimetastatic activity of direct-acting anticoagulants, the most significant, in our opinion, are suppression of lymphangiogenesis, inhibition of heparanase and P-selectin, suppression of angiogenesis.
Given the fact that new, safer agents are emerging among direct-acting anticoagulants, further research their impact on metastatic processes is appropriate.