Evaluation of: Beavis PA, Divisekera U, Paget C et al. Blockade of A2A receptors potently suppresses the metastasis of CD73(+) tumors. Proc. Natl Acad. Sci. USA 110(36), 14711-14716 (2013). CD73 is becoming an emerging therapeutic target for the prevention of tumor growth and metastasis. However, the mechanism by which CD73 promotes tumor metastasis is unclear. Beavis et al. evaluated the efficacy of A2A and A2B adenosine receptor antagonists in inhibiting the metastasis of tumors expressing CD73, either endogenously or ectopically. They demonstrate distinct mechanisms whereby A2A versus A2B adenosine receptors could contribute to CD73(+) tumor metastasis. As A2Areceptor (R)/A2BR antagonists have been tested in clinical trials in other disease settings, this study highlights the potential therapeutic application of an A2AR/A2BR blockade strategy for treatment of CD73(+) metastatic tumors.