Tumor-platelet cross talk in cancer: mechanisms, thrombotic risk, and translational opportunities

Platelets are recognized as mediators of cancer progression, extending beyond hemostasis to influence tumor growth, metastatic dissemination, immune evasion, and thrombotic complications. Tumors remodel platelets through thrombocytosis and tumor cell-induced platelet aggregation, and locally through tumor microenvironment cues that reprogram platelet function. These changes enable platelets to shield tumor cells, support epithelial-mesenchymal transition, promote angiogenesis and vascular remodeling, and establish immunosuppressive niches that promote metastasis. Platelets also drive both venous and arterial cancer-associated thrombosis (CAT) through procoagulant platelet states, platelet-derived extracellular vesicles, and cross talk with the endothelium and innate immune pathways. Platelet RNA signatures and emerging proteomic/multiomic profiling show promise for cancer detection, classification, and treatment monitoring. Preclinical and translational studies suggest that antiplatelet strategies (eg, aspirin, purinergic receptor P2Y type 12 inhibition) can modulate metastatic and thromboinflammatory pathways, motivating platelet-targeted interventions that mitigate bleeding risk. This review synthesizes platelet-tumor cross talk, linking tumor progression with CAT and vascular events, and highlights emerging platelet-based biomarkers and therapeutic opportunities.