Molecular regulators of thromboinflammation and angiogenesis in pediatric cancer: emerging roles of noncoding RNAs, epigenetics, and extracellular vesicles - narrative review.

Pediatric cancers, although less prevalent, remain a significant cause of mortality among children worldwide. Thromboinflammation arises from a complex dysregulation of inflammation and hemostasis, leading to tissue injury and cell death. Angiogenesis, the formation of new blood vessels, is influenced by inflammation. Both processes are closely linked to the progression of various tumors. Emerging evidence increasingly highlights the pivotal role of certain molecular markers in stimulating thromboinflammatory and angiogenic pathways in several types of pediatric cancers, including gliomas, other brain tumors, retinoblastoma, leukemia, lymphoma, and other solid malignancies. Current studies show that noncoding RNAs (ncRNAs), extracellular vesicles (EVs), and epigenetic dysregulation of key biological pathways in specific genes contribute to alterations in the tumor microenvironment. These changes are crucial for tumor initiation, progression, and dissemination through immune-mediated mechanisms that promote thromboinflammation and angiogenesis. The detailed identification and assessment of the expression profiles of these markers hold growing potential to support the diagnosis of various pediatric cancers, provide better prognostic stratification, and guide targeted therapeutic approaches. Therefore, integrating this knowledge into existing strategies for diagnosis, staging, and treatment - especially through liquid biopsy based on EVs and RNA signatures - may enable earlier and more precise interventions. This has the potential to positively impact long-term survival and quality of life.