Targeted Liquid Biopsy for Brain Tumors

Cerebrospinal fluid (CSF) is a promising source of molecular biomarkers in the detection and monitoring of brain malignancies. Unlike peripheral blood, where biomarker detection is hindered by the blood-brain barrier and the complex nature of biofluids, CSF offers a more direct and enriched source of tumor-derived markers, including circulating tumor DNA (ctDNA), microRNA (miRNA), proteins, and extracellular vesicles (EVs). These biomarkers, originating from brain tumor cells, are often more concentrated in CSF than in peripheral blood due to the proximity of CSF to the central nervous system (CNS). The presence of ctDNA in CSF is notably higher than in plasma, making CSF an advantageous medium for liquid biopsy in brain tumor patients. Traditional liquid biopsy approaches relying on peripheral venous blood samples often face challenges in detecting low concentrations of tumor-derived biomarkers. The direct contact of CSF with the CNS minimizes background noise, potentially enhancing the accuracy and sensitivity of diagnostic assays. Despite the barriers posed by the blood-brain barrier and other physiological factors that limit biomarker levels in the systemic circulation, CSF's unique position within the CNS allows for more effective biomarker collection. While peripheral blood remains the standard medium for liquid biopsy in oncology, the proximity of CSF to brain tumors suggests it may offer superior diagnostic capabilities. Emerging evidence from non-CNS malignancies indicates that collecting biofluids closer to the tumor site can significantly improve biomarker detection. Although this approach has been well-documented in other solid tumors, its application to CNS malignancies remains underexplored. This study hypothesizes that targeted blood sampling from CNS tumor-draining veins could similarly enhance biomarker detection, thereby increasing the sensitivity and efficacy of liquid biopsy techniques in diagnosing and monitoring brain malignancies.