Liquid Biopsy for Glioblastoma: Emerging Biomarkers, Clinical Utility, Current Challenges and Future Perspectives - A Narrative Review
Background Glioblastoma (GBM) is the most aggressive primary malignant brain tumor in adults and is characterized by extensive molecular and spatial heterogeneity, diffuse infiltration, and frequent recurrence. Current diagnosis and disease monitoring rely primarily on tissue pathology and magnetic resonance imaging (MRI). However, tissue sampling is invasive and may not fully capture the heterogeneous and evolving molecular landscape of the tumor, while MRI may have difficulty distinguishing recurrent disease from treatment-related changes. Liquid biopsy has emerged as a minimally invasive approach for detecting tumor-derived material in biological fluids and may provide opportunities for repeated molecular assessment throughout the disease course. Objective This narrative review summarizes the current evidence regarding liquid biopsy in glioblastoma, with emphasis on circulating tumor DNA, cell-free DNA, circulating tumor cells, microRNAs, extracellular vesicles, and other circulating biomarkers. It further examines their potential applications in molecular characterization, diagnosis, prognostic assessment, treatment-response monitoring, and detection of recurrence. Methods A narrative literature review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Literature addressing glioblastoma, liquid biopsy, circulating tumor DNA, cell-free DNA, circulating tumor cells, microRNAs, extracellular vesicles, exosomes, cerebrospinal fluid biomarkers, treatment monitoring, and recurrence was identified and critically synthesized. Original research studies, systematic reviews, meta-analyses, and relevant contemporary reviews were considered. Particular attention was given to evidence regarding blood- and cerebrospinal-fluidderived biomarkers and their potential clinical applications. Results Current evidence indicates that liquid biopsy may provide minimally invasive molecular and longitudinal information in patients with glioblastoma. Circulating tumor DNA and cell-free DNA have been investigated for detection of tumorassociated genetic and epigenetic alterations, while circulating tumor cells, microRNAs, and extracellular vesicles represent additional potential sources of diagnostic and prognostic information. Cerebrospinal fluid may provide greater detectability of tumor-derived material than peripheral blood in selected patients, whereas blood-based approaches offer advantages for repeated and less invasive sampling. Emerging studies also suggest potential applications in monitoring treatment response, tumor evolution, and recurrence. Nevertheless, clinical implementation remains constrained by low circulating tumor fractions, the blood–brain barrier, tumor heterogeneity, methodological variability, and limited prospective validation. Conclusion Liquid biopsy represents a promising complementary approach to conventional tissue pathology and neuroimaging in glioblastoma. Its greatest future value may lie in longitudinal molecular monitoring and integration with MRI, radiomics, artificial intelligence, and other molecular profiling approaches. Standardization of analytical methods and prospective multicenter validation will be necessary before liquid biopsy can be routinely incorporated into clinical practice.