(A) Platelets provide protection to circulating tumor cells (CTCs) by forming a physical shield around them, which prevents natural killer (NK) cells from attacking. In addition, platelets transfer their MHC-I molecules onto the membranes of CTCs, enabling the tumor cells to downregulate their own MHC-I expression. This mechanism allows CTCs to evade T cell detection while avoiding NK cell-mediated elimination through “missing self” recognition. Furthermore, platelets can hinder NK cell recognition of CTCs by activating NKG2D receptors. Platelets also facilitate the interaction between CTCs and neutrophil extracellular traps (NETs), which aids in CTC distribution and adhesion. Through the activation of the RhoA/YAP signaling pathway, platelets enhance the resistance of CTCs to apoptosis. (B) Platelets prime endothelial cells for adhesion through CD40/CD154 interactions or the release of microparticles. This interaction promotes the capture of CTCs by the endothelial lining, reducing their rolling velocity. Integrins mediate the adhesion of the platelet–CTC complex to the endothelium. Additionally, ATP released by platelets interacts with the P2Y2 receptor on endothelial cells, contributing to the closure of the endothelial barrier. Reproduced from Lin Zhou et al. The critical role of platelet in cancer progression and metastasis. European Journal of Medical Research 2023 Sep 28;28:385. http://creativecommons.org/licenses/by/4.0/.

Platelets play a pivotal role in cancer detection and metastasis, serving both as novel liquid biopsy biomarkers and as versatile carriers in nanomedicine. Tumor-educated platelets (TEPs) undergo molecular alterations influenced by the tumor microenvironment, with their RNA profiles—including mRNA, circular RNA, and long noncoding RNA—offering potential for early cancer detection, prognosis, and treatment monitoring. Additionally, platelet-derived extracellular vesicles (PEVs) and activation markers (e.g., P-selectin, CD40L) further enhance their diagnostic utility. However, standardization of platelet biomarker analysis remains a challenge for clinical implementation. Concurrently, nanotechnology is leveraging the natural biocompatibility and targeting properties of platelets to develop platelet-based drug delivery systems and bioinspired nanomaterials, improving therapeutic precision and efficacy. Moreover, artificial intelligence (AI)-driven biomarker analysis is refining TEP and PEV profiling, accelerating advances in precision oncology. Future research should focus on establishing standardized protocols, optimizing platelet-based nanomedicine, and integrating AI to enhance diagnostic accuracy and therapeutic efficacy. By bridging biological insights with clinical applications, platelets hold significant promise as transformative tools in precision oncology.

Article Access: https://doi.org/10.1002/mba2.70010

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