rivaroxaban and Triple-Negative-Breast-Neoplasms

Essentials Factor Xa (FXa)-targeting direct oral anticoagulants (DOACs) reduce venous thromboembolism (VTE) The effects of FXa-targeting DOACs on cancer progression remain to be studied In xenograft models, a FXa-targeting DOAC did not inhibit breast cancer growth and metastasis A thrombin-targeting DOAC, dabigatran, also did not inhibit breast cancer growth and metastasis ABSTRACT: Background Factor Xa-targeting DOACs were recently found to reduce recurrent VTE efficiently in cancer patients when compared to the standard treatment with low-molecular-weight heparins (LMWHs). While the anticancer effects of LMWHs have been extensively studied in preclinical cancer models, the effects of FXa-targeting DOACs on cancer progression remain to be studied. Objective We investigated whether the FXa-targeting DOAC rivaroxaban and the thrombin-targeting DOAC dabigatran etexilate (DE) affected human breast cancer growth and metastasis in orthotopic xenograft models. Methods/results Mice that were put on a custom-made chow diet supplemented with rivaroxaban (0.4 or 1.0 mg/g diet) or dabigatran etexilate (DE) (10 mg/g diet) showed prolonged ex vivo coagulation times (prothrombin time [PT] and activated partial thromboplastin time [aPTT] assay, respectively). However, rivaroxaban and DE did not inhibit MDA-MB-231 tumor growth and metastasis formation in lungs or livers of 7-week-old fully immunodeficient NOD/SCID/ƴ

Topics: Animals; Anticoagulants; Antithrombins; Breast Neoplasms; Cell Line, Tumor; Dabigatran; Disease Progression; Factor Xa Inhibitors; Female; Humans; Mice; Mice, Inbred NOD; Mice, SCID; Neoplasm Metastasis; Rivaroxaban; Triple Negative Breast Neoplasms; Venous Thromboembolism; Xenograft Model Antitumor Assays