Platelet surface receptors in cancer progression and metastasis: from molecular insights to therapeutic opportunities

Platelet surface receptors play essential roles in cancer progression and metastasis by mediating platelet‒tumor cell interactions. Among these receptors, CLEC-2 and PD-L1 specifically mediate platelet–tumor interactions, whereby CLEC-2 promotes tumor growth and induces epithelial–mesenchymal transition (EMT), while PD-L1 facilitates immune evasion by malignant cells. Additionally, platelet receptors involved in physiological hemostasis, such as αIIbβ3, GPVI, P-selectin, P2Y12, and PAR1, can also facilitate tumor growth and metastatic processes through their interactions with tumor cells. In the early stages of tumor development, GPVI, P-selectin, and P2Y12 receptors are engaged, whereas during angiogenesis, αIIbβ3, P-selectin, P2Y12, and PAR1 receptors become active. In the metastatic phase, αIIbβ3, GPVI, P-selectin, and PAR1 receptors are implicated. Targeting these specific platelet receptors has demonstrated significant therapeutic potential in cancer treatment. Notably, in certain cancers, specific receptor inhibitors targeting CLEC-2, P-selectin, and P2Y12 have been shown to effectively inhibit tumor growth and metastasis, with favorable bleeding risk profiles. In this review, we present a detailed picture of the roles of platelet receptors in cancer progression and metastasis, elucidate the underlying molecular mechanisms, and evaluate the therapeutic potential of receptor-targeted therapies in limiting tumor dissemination.