Key result
In animal models, DOAC monotherapy decreased tumor growth at implanted and metastatic sites in 18.8% and 20.0% of experiments, respectively, but increased growth in 6.3% and 20.0% of experiments.
Why the study?
DOACs are first-choice thromboprophylaxis in low-bleeding-risk cancer patients, and their potential anti-tumor effects have been investigated in animal cancer models.
Does DOAC monotherapy affect cancer growth and metastasis in animal models?
Systematic Review (n=9)
Does DOAC monotherapy affect cancer growth and metastasis in animal models?
In animal models, the effect of DOAC monotherapy on cancer growth and metastasis is highly variable and depends on the timing of treatment and the specific cancer model used.
Answers are grounded in this paper and cite their sources.
Inconsistent effects across animal models; leaves open any anti-tumor role for DOACs beyond anticoagulation in cancer.
BACKGROUND: Direct oral anticoagulants (DOACs) are now the first choice thromboprophylaxis in cancer patients who do not have a high risk of bleeding. In addition to the anticoagulant effects, potential anti-tumor effects of DOACs have also been studied in animal cancer models. In this study, we summarize the effects of DOACs on cancer growth and metastasis in animal models through a systematic review with a qualitative analysis. METHODS: PubMed, EMBASE and Web of Science were systematically searched for original studies that describe animal models of cancer in which one of the experimental groups received DOAC monotherapy, and which reported quantitatively on primary tumor or metastases. RESULTS: Nine studies - reporting a total of 19 animal experiments - met the inclusion criteria. These 19 experiments included spontaneous cancer (n = 2), carcinogenicity (n = 2), xenograft (n = 7) and syngeneic (n = 8) models, encompassing orthotopic (n = 7), subcutaneous (n = 5), intraperitoneal (n = 1) and intravenous (n = 2) injection of cancer cells and included treatments with the DOACs ximelagatran (n = 4), dabigatran etexilate (n = 6) and/or rivaroxaban (n = 11). DOAC treatment decreased tumor growth at implanted and metastatic site in 18.8% (3/16) and 20.0% (3/15) of the experiments, respectively. Conversely, DOACs increased tumor growth at implanted and metastatic site in 6.3% (1/16) and 20.0% (3/15) of the experiments, respectively. CONCLUSION: DOAC monotherapy resulted in neoplastic changes in a rat carcinogenicity study, showed a lack of effect in mouse xenograft models, while the effect on cancer growth and metastasis in mouse syngeneic models depended on the timing of DOAC treatment and type of cancer model used.
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Najidh et al. (2020) conducted a systematic review in Cancer (animal models) (n=9). Direct oral anticoagulants (DOACs) was evaluated on Tumor growth at implanted and metastatic site. In animal models, DOAC monotherapy decreased tumor growth at implanted and metastatic sites in 18.8% and 20.0% of experiments, respectively, but increased growth in 6.3% and 20.0% of experiments.
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