Chahardehi, Amir ModarresiFaraji, NikiEmtiazi, NikooNasiri, RezaDaghagheleh, MaryamMohammadaein, HeliaTavakoli, Marziye Ranjbar2025-05-252025-05-2520252667-2421https://doi.org/10.1016/j.ibneur.2025.04.007Brain tumors provide considerable diagnostic and treatment challenges due to their intricate nature and the hazards linked to direct tissue biopsies. Owing to the restricted sensitivity and specificity of conventional procedures, new techniques like liquid biopsy have garnered attention. Circulating tumor DNA (ctDNA), present in physiological fluids such as cerebrospinal fluid (CSF) and plasma, has emerged as a viable instrument for noninvasive tumor characterization. Hence, advancements in next-generation sequencing (NGS) and digital PCR have enhanced the sensitivity of ctDNA detection, rendering it a feasible method for monitoring tumor dynamics and evaluating therapy responses. Research indicates that ctDNA strongly correlates with tumor heterogeneity, providing a superior alternative to single-site tissue biopsies. CSF, due to its proximity to the brain, offers elevated amounts of ctDNA for examination relative to plasma, particularly in central nervous system (CNS) cancers. Research indicates that ctDNA can detect actionable mutations, forecast little residual illness, and enable real-time monitoring of disease development and resistance. Notwithstanding these advantages, difficulties, including poor ctDNA yield and heterogeneity in detection methodologies persist. This review examines the clinical efficacy of ctDNA in brain tumor diagnosis, emphasizes technical developments in ctDNA analysis, and stresses the necessity for standardized methods. Comprehending the capabilities and constraints of ctDNA can facilitate the development of more accurate, individualized therapy approaches in neuro-oncology.eninfo:eu-repo/semantics/closedAccessBrain TumorCell Free DNACirculating Tumor DNAGlioblastomaGliomaArticle10.1016/j.ibneur.2025.04.0072-s2.0-105004407067