The coagulation system constitutes an important facet of the unique vascular microenvironment in which primary and metastatic
brain tumors evolve and progress. While
brain tumor cells express
tissue factor (TF) and other effectors of the coagulation system (coagulome), their propensity to induce local and peripheral
thrombosis is highly diverse, most dramatic in the case of
glioblastoma multiforme (GBM), and less obvious in pediatric
tumors. While the immediate medical needs often frame the discussion on current clinical challenges, the coagulation pathway may contribute to
brain tumor progression through subtle, context-dependent, and non-
coagulant effects, such as induction of
inflammation, angiogenesis, or by responding to iatrogenic insults (e.g. surgery). In this regard, the emerging molecular diversity of
brain tumor suptypes (e.g. in
glioma and
medulloblastoma) highlights the link between oncogenic pathways and the
tumor repertoire of coagulation system regulators (coagulome). This relationship may influence the mechanisms of spontaneous and therapeutically provoked
tumor cell interactions with the coagulation system as a whole. Indeed, oncogenes (EGFR, MET) and
tumor suppressors (PTEN, TP53) may alter the expression, activity, and vesicular release of
tissue factor (TF), and cause other changes. Conversely, the
coagulant microenvironment may also influence the molecular evolution of
brain tumor cells through selective and instructive cues. We suggest that effective targeting of the coagulation system in
brain tumors should be explored through molecular stratification, stage-specific analysis, and more personalized approaches including thromboprophylaxis and adjuvant treatment aimed at improvement of patient survival.