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.
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.
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...
Show moreFactor 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.
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.
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/ƴC
−/− (NSG) mice.
Comparable data were obtained for rivaroxaban‐treated mice when using NOD‐SCID
mice. Rivaroxaban and DE treatment also did not significantly inhibit tumor growth
and metastasis formation when using another human triple negative breast cancer
(TNBC) cell line (HCC1806) in NOD‐SCID mice. The FXa and thrombin‐induced gene
expression of the downstream target CXCL8 in both cell lines, but FXa and thrombin,
did not significantly stimulate migration, proliferation, or stemness in vitro.
Although effectively inhibiting coagulation, the DOACs rivaroxaban and
DE did not inhibit orthotopic growth and metastasis of human TNBC. It remains to be
investigated whether DOACs exert antitumorigenic effects in other types of cancer.
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