Emerging Biomarkers for Brain Tumors: Advances in Early Detection and Therapeutic Monitoring

Abstract

Brain tumors, including primary and metastatic brain tumors, remain a major clinical challenge because of their biological heterogeneity, aggressive behavior, and limited treatment options. Early diagnosis, accurate prognostication, and continuous monitoring are essential for improving patient outcomes. Recent advances in molecular biology and liquid biopsy technologies have identified several promising biomarkers with potential clinical applications. This review summarizes emerging genetic, epigenetic, metabolic, and circulating biomarkers for brain tumors, with particular emphasis on extracellular vesicles (EVs) and cerebrospinal fluid (CSF). Established molecular markers, including isocitrate dehydrogenase (IDH) mutations, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, H3K27M, epidermal growth factor receptor (EGFR) amplification, TP53 and BRAF mutations, and TERT promoter mutations, provide valuable information for tumor classification, prognosis, and therapeutic decision-making. Additional biomarkers such as S100B, YKL-40, microRNAs, choline, and lactate may contribute to disease monitoring and assessment of tumor activity. Advances in next-generation sequencing and liquid biopsy have further enhanced the ability to detect tumor-specific molecular alterations and monitor tumor evolution. EVs are particularly promising because they transport proteins, lipids, DNA, and RNA and may facilitate both biomarker detection and targeted drug delivery across the blood-brain barrier. CSF represents another valuable biomarker source because of its close proximity to brain tumors and higher concentration of tumor-derived molecules compared with peripheral blood. Despite these advances, challenges related to assay standardization, sensitivity, specificity, sampling, and clinical validation remain. Integrating molecular biomarkers, EVs, CSF analysis, and advanced genomic technologies may ultimately enable more accurate diagnosis, personalized treatment, and real-time monitoring of brain tumors.