Figure 7. Inhibition of ovarian tumor progression by dabigatran etexilate.

Thrombin has many activities that promote cancer progression. Thrombin can induce TGF-β via platelet activation and PAR-1 signaling in the tumor epithelial cells. Elevated ascites levels of TGF-β, VEGF, and MCP-1 impact the recruitment and expansion of myeloid derived immunosuppressive cells, such as MDSCs and DCs. These myeloid derived cell populations, which can also be directly modulated by thrombin via PAR-1 signaling, impair T-cell and natural killer cell function contributing to the immunosuppressive microenvironment. Dabigatran etexilate directly inhibits thrombin, disrupting many of these protumorigenic pathways.