Therapeutic potential of aspirin in metastatic brain disease: A narrative review bridging evidence from systemic cancers to brain metastasis

Background Acetylsalicylic acid (aspirin) is a widely used medication with antipyretic, anti-inflammatory, and antiplatelet effects. It also exhibits antitumor properties by enhancing immune responses, downregulating proinflammatory cytokines, and interfering with platelet–tumor cell interactions that promote metastatic dissemination. Identifying effective, safe interventions for brain metastases (BMs) remains a major clinical challenge. Objectives This narrative review synthesizes mechanistic, preclinical, clinical, and safety evidence on aspirin's potential role in preventing or modulating brain metastasis and proposes possible preventive and adjuvant strategies for future investigation. Discussion The development of BMs involves tumor-derived factors, extracellular vesicles, and recruited host cells that remodel the brain microenvironment into a premetastatic niche. Platelet activation and the COX-1/TXA 2 axis promote platelet–tumor cell aggregates, immune evasion, and endothelial adhesion—key steps in metastatic seeding. Aspirin may inhibit these processes by (1) irreversibly blocking platelet COX-1 (reducing TXA 2 and aggregation), (2) lowering prostaglandin E 2 (PGE 2 )–mediated immunosuppression, and (3) preserving blood–brain barrier (BBB) integrity. Preclinical and retrospective clinical studies provide supportive but heterogeneous evidence across cancer types. Combination strategies—aspirin with radiotherapy, antioxidants (e.g., ascorbic acid), or immunotherapy—are biologically plausible and supported by limited data. Major safety concerns remain, particularly bleeding risk and intracranial hemorrhage in patients with intracranial disease. Conclusion Aspirin is a low-cost, biologically plausible adjunct for metastasis prevention. However, direct evidence in brain-metastasis settings is limited. Prospective trials with mechanistic biomarkers and careful safety monitoring are required to determine optimal dosing, timing, patient selection, and combination strategies.