Given the site-specific nature of cancer, along with the specific mechanisms that different cancer cells can develop to activate platelets and viceversa the final ATP/ADP effect will depend on the P2 receptor subtypes expressed and activated (Burnstock and Di Virgilio, 2013). Thus, an improved knowledge of the signaling induced by the activation of P2Y12R during the interaction of platelets with cancer cells is needed. Interestingly, the PLATelet inhibition and patient Outcomes (PLATO) study showed that ticagrelor exerts an anti-inflammatory effect higher than clopidogrel (Thomas and Storey, 2015). Ticagrelor can inhibit the adenosine transporter ENT1 (Cattaneo et al., 2014). This increases the extracellular concentration of the nucleoside, which is a recognized modulator of inflammatory and immune responses. Thus, clinical research, focused on targeted biomarkers, is needed to clarify the role of P2Y12R-antagonists in these mechanisms, which are relevant in cancer development and metastasis.