The potential contribution of P2Y12 receptor in cancer and metastasis. P2Y12 receptor (R) antagonists include thienopyridines, such as ticlopidine, clopidogrel and prasugrel, that irreversibly inhibit P2Y12R upon metabolic conversion into active metabolites by the hepatic cytochrome P-450 system (Cattaneo, 2010; Schrör et al., 2012) and ticagrelor, cangrelor and elinogrel, which reversibly and directly bind the receptor without any need for bioactivation (Cattaneo, 2010; Schrör et al., 2012). By targeting P2Y12R these drugs may contribute to constrain metastasis development through the prevention of platelet activation by ADP. Once activated, platelet-derived PGE2 and a direct platelet-tumor cell interaction synergize to promote epithelial-mesenchymal transition (EMT), migration and metastasis formation (Guillem-Llobat et al., 2016). Moreover, like platelets, cancer cells have been shown to release a significant amount of ATP (Beigi et al., 1999; Pellegatti et al., 2008; Burnstock and Di Virgilio, 2013), which is hydrolyzed into ADP through the activity of the ecto-enzymes CD39 (Bakker et al., 1994; Robson et al., 2006; Burnstock, 2017). Extracellular ADP, deriving from both activated platelets and cancer cells, in turn could activate P2Y12R expressed both in platelets and in malignant cells, thus triggering a vicious circle, which could contribute to cancer progression and dissemination.