Tumor-Educated Platelets: a New Frontier in Platelet Derivatives clinical applications

Platelets, long known as key effectors of hemostasis, have progressively emerged as central actors in regenerative medicine through Non-Transfusional Use Hemocomponents (NTUHs) and Platelet Derivatives (PDs). Recently, Tumor-Educated Platelets (TEPs) have been proposed as alternative biosource for oncological liquid biopsy (LB). This Doctoral Project explored whether platelets could provide diagnostic and prognostic value in oncology, complementing their established therapeutic role, through three integrated assessments: a Bibliometric Analysis and Umbrella Review of NTUHs applications worldwide, a Health Economic analysis of LB, and a pilot clinical study on TEPs.The Bibliometric Analysis and Umbrella Review included 1,071 and 1,021 articles, respectively, identifying 21 medical specialties. Compared to standard of care, 75% improved outcomes and 24% comparable results are obtained, with extremely rare serious adverse events. However, heterogeneous nomenclature, frequent methodological weaknesses and substantial reporting bias limited the robustness of the evidence.The Health Economic Analysis included 21 cost-effectiveness studies on LB in oncology. Incremental Cost-Effectiveness Ratios were converted to 2024 EUR and normalized using a ΔWTP% metric against multiple Willingness-To-Pay (WTP) thresholds. Doing so, LB resulted on average cost-effective or even cost-saving when carefully targeted. An Italian scenario based on national GDP suggested positive outcomes in ~95% of evaluated conditions, supporting LB integration into clinical practice with potential benefits for all the stakeholders.Finally, the still ongoing pilot study on 12 lung cancer and 12 melanoma patients preliminary showed clear qualitative differences between healthy platelets and TEPs. By Scanning Electron Microscopy (SEM), the latter displays chaotic, densely interconnected patterns and distinct phenotypes. Pre-post visual comparisons suggested possible prognostic signals but also highlighted marked morphological heterogeneity.Overall, this Project supports PDs as a widely used yet still fragile platform, LB as economically valuable, and TEPs as promising candidates for future oncological LB applications, warranting further validation.