Authors :
Usha Topalkatti; Jhansi Mani Mahadeva
Volume/Issue :
Volume 11 - 2026, Issue 8 - August
Google Scholar :
https://tinyurl.com/2nunzfdf
Scribd :
https://tinyurl.com/4b84f2s4
DOI :
https://doi.org/10.38124/ijisrt/26aug582
Note : A published paper may take 4-5
working days from the publication date to appear in PlumX Metrics, Semantic Scholar, and
ResearchGate.
Abstract :
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.
Keywords :
Glioblastoma; Liquid Biopsy; Circulating Tumor DNA; Cell-Free DNA; Circulating Tumor Cells; MicroRNA; Extracellular Vesicles; Cerebrospinal Fluid; Biomarkers; Precision Medicine.
References :
- Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016.
- Baxter PA, et al. Significance of liquid biopsy in glioblastoma—a review. J Biotechnol. 2019.
- Miller AM, Shah RH, Pentsova EI, et al. Tracking tumour evolution in glioma through liquid biopsies of cerebrospinal fluid. Nature. 2019.
- Mair R, Mouliere F, Smith CG, et al. Measurement of plasma cell-free mitochondrial tumor DNA improves detection of glioblastoma in patient-derived orthotopic xenograft models. Cancer Res. 2019.
- Miller AM, et al. Analysis of cell-free circulating tumor DNA in 419 patients with glioblastoma and other primary brain tumors. Clin Cancer Res. 2019.
- Sullivan RJ, et al. Liquid biopsy in glioblastoma: opportunities, applications and challenges. 2019.
- Nabors LB, et al. Extracellular vesicles as a platform for liquid biopsy in glioblastoma patients.
- Miller AM, et al. Cerebrospinal fluid circulating tumor DNA as a liquid biopsy for central nervous system malignancies. Curr Opin Oncol. 2020.
- Friedman JS, Hertz CA, Karajannis MA, Miller AM. Tapping into the genome: the role of CSF ctDNA liquid biopsy in glioma. Neurooncol Adv. 2022.
- Garrido-Castro AC, et al. Liquid biopsy and glioblastoma. 2023.
- Mouliere F, et al. Clinical utility of plasma cell-free DNA in gliomas. Neuro-Oncology Advances. 2022.
- Tumor-Derived Biomarkers in Liquid Biopsy of Glioblastoma. 2022.
- The Current Landscape of Glioblastoma Biomarkers in Body Fluids. 2023.
- Highly Sensitive EGFRvIII Detection in Circulating Extracellular Vesicle RNA of Glioma Patients. 2022.
- Circulating extracellular vesicles as biomarker for diagnosis, prognosis, and monitoring in glioblastoma patients. 2024.
- Chandran VI, et al. Extracellular vesicles in glioblastoma: a challenge and an opportunity. NPJ Precis Oncol. 2024;8:103.
- Cerebrospinal Fluid Liquid Biopsies in the Evaluation of Adult Gliomas. 2024.
- Circulating Tumor DNA in Adults With Glioma: A Systematic Review and Meta-Analysis of Biomarker Performance. 2022.
- Plasma ctDNA liquid biopsy of IDH1, TERTp, and EGFRvIII mutations in glioma. 2024.
- Impact of Higher Cell-Free DNA Yields on Liquid Biopsy Testing in Glioblastoma Patients. 2025.
- Aibaidula A, et al. Plasma extracellular vesicles as liquid biopsies for glioblastoma: biomarkers, subpopulation enrichment, and clinical translation. Int J Mol Sci. 2025;26:11686.
- Niznik T, et al. Exploring the diagnostic test accuracy of microRNAs as potential biomarkers for glioblastoma: systematic review and meta-analysis. Neurosurgery. 2025.
- Liquid Biopsy-Derived Tumor Biomarkers for Clinical Applications in Glioblastoma. 2025.
- Extracellular vesicles as liquid biopsy tools for personalized therapeutic goals in glioblastoma. Brain. 2026.
- Baethge C, Goldbeck-Wood S, Mertens S. SANRA—a scale for the quality assessment of narrative review articles. Res Integr Peer Rev. 2019;4:5.
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.
Keywords :
Glioblastoma; Liquid Biopsy; Circulating Tumor DNA; Cell-Free DNA; Circulating Tumor Cells; MicroRNA; Extracellular Vesicles; Cerebrospinal Fluid; Biomarkers; Precision Medicine.