Microscopic view of liquid biopsy components with neural network overlay.

Liquid Biopsies: The Future of Brain Tumor Diagnosis?

Elliot Brynn in Health & Wellness December 2025 • 4 min read.

"Discover how liquid biopsies are revolutionizing brain tumor diagnosis and treatment monitoring, offering a less invasive approach with potentially greater insights."

The standard methods for monitoring and diagnosing central nervous system tumors may soon be revolutionized by minimally invasive techniques. A promising method for establishing diagnoses and tracking treatment response is the liquid biopsy, which involves sampling blood or cerebrospinal fluid.

The traditional method of evaluating how tumors respond to treatment depends heavily on neuroimaging. However, it can be challenging to correlate therapeutic response with imaging results because the intervention could impact the imaging characteristics of the tumor. For example, chemoradiation may result in increased contrast enhancement, a phenomenon known as pseudoprogression, which indicates changes to the local blood-brain barrier or radiation necrosis. Conversely, antiangiogenic drugs can alter the permeability of tumor vasculature and reduce contrast enhancement without actually reducing the disease burden.

Liquid biopsies are especially interesting for glioblastoma (GBM) tumors for a few compelling reasons. Unlike many other tumors, the biopsy procedure carries a significant amount of risk. There may be substantial brain swelling in and around the tumor, for instance. Even a small amount of hemorrhage along the biopsy tract could endanger the patient's neurological function or even their life. In addition, brain biopsies are extremely difficult when it comes to obtaining longitudinal samples or prospectively collecting tissue samples repeatedly because of the risk involved with the biopsy itself. It is more difficult to track treatment response, observe clonal evolution to find new susceptibilities or acquired mechanisms of resistance to therapy, and distinguish tumor recurrence from pseudoprogression when longitudinal samples are difficult to obtain.

How Do Liquid Biopsies Work in Brain Tumors?

Microscopic view of liquid biopsy components with neural network overlay.

Liquid biopsies analyze circulating tumor cells (CTCs), cell-free nucleic acids, and extracellular vesicles (EVs). These components, found in blood or cerebrospinal fluid, offer insights into the tumor's characteristics without invasive procedures.

Each component offers unique advantages:

Circulating Tumor Cells (CTCs): These cells, shed from the primary tumor, can reveal genetic mutations and expression patterns, offering a snapshot of the tumor's characteristics.
Cell-Free Tumor DNA (ctDNA): Analyzing ctDNA can identify tumor-specific mutations and track the tumor's evolution over time. However, technical challenges exist due to the low concentration of nucleic acid in biofluids.
Extracellular Vesicles (EVs): EVs, including exosomes, transport RNA, DNA, and proteins, providing a comprehensive view of the tumor's molecular profile.

Integrating the analysis of CTCs, EVs, and ctDNA can potentially characterize the global tumor genome and transcriptome [5], which may not be fully captured by focal sampling of a lesion by biopsy [4].

The Future of Liquid Biopsies

Liquid biopsies represent a significant advancement in brain tumor diagnostics, offering a non-invasive method to monitor disease progression and treatment response. As technology advances, these techniques promise to become more refined, providing clinicians with valuable insights for personalized treatment strategies. Future research will focus on improving signal detection, standardizing procedures, and integrating multi-omic data to enhance the accuracy and clinical utility of liquid biopsies. Despite existing challenges, liquid biopsies hold immense potential for transforming brain tumor care, improving patient outcomes through more precise and adaptive treatment approaches.

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Everything You Need To Know

What exactly are liquid biopsies, and how are they used for brain tumors?

Liquid biopsies are a minimally invasive method used to diagnose and monitor brain tumors by analyzing samples from blood or cerebrospinal fluid. This technique focuses on components like circulating tumor cells (CTCs), cell-free tumor DNA (ctDNA), and extracellular vesicles (EVs) to provide insights into the tumor's characteristics without the need for traditional, riskier biopsies. This is particularly important in brain tumors like glioblastoma (GBM) where traditional biopsies can be dangerous due to the risk of brain swelling and hemorrhage.

Why are liquid biopsies considered a significant advancement over traditional methods for monitoring and diagnosing brain tumors?

Liquid biopsies offer a less invasive way to gather information about brain tumors compared to traditional methods like neuroimaging and tissue biopsies. This is especially significant because traditional methods may not accurately reflect the tumor's response to treatment. For instance, treatments like chemoradiation can cause pseudoprogression, where imaging shows increased contrast enhancement, but it isn't actually tumor growth. Similarly, antiangiogenic drugs can reduce contrast enhancement without reducing the actual disease burden. Liquid biopsies can provide a more direct and real-time assessment of the tumor's characteristics and response to therapy.

What specific components are analyzed in liquid biopsies, and what type of information does each component provide about the tumor?

Liquid biopsies analyze three primary components: circulating tumor cells (CTCs), cell-free tumor DNA (ctDNA), and extracellular vesicles (EVs). Circulating tumor cells, shed from the primary tumor, reveal genetic mutations and expression patterns. Cell-free tumor DNA helps identify tumor-specific mutations and tracks the tumor's evolution. Extracellular vesicles, including exosomes, transport RNA, DNA, and proteins, offering a comprehensive view of the tumor's molecular profile. By integrating the analysis of all these components, clinicians can gain a more complete understanding of the tumor.

What are circulating tumor cells (CTCs), and why are they important in the context of liquid biopsies for brain tumors?

Circulating tumor cells (CTCs) are significant because they are cells that have detached from the primary tumor and are circulating in the blood or cerebrospinal fluid. Analyzing CTCs allows doctors to gain insights into the genetic mutations and expression patterns present in the tumor. This information helps in understanding the tumor's characteristics and can guide treatment decisions by providing a snapshot of the tumor's features at a specific point in time. This can be crucial for tailoring treatment strategies to the specific genetic makeup of the tumor.

What are the current limitations or challenges associated with liquid biopsies, and how are researchers working to overcome them?

While liquid biopsies show great promise, there are challenges to overcome. One significant challenge is improving the detection of tumor-specific signals in blood or cerebrospinal fluid, as the concentration of circulating tumor cells (CTCs) and cell-free tumor DNA (ctDNA) can be very low. Additionally, there is a need for standardizing the procedures for collecting and analyzing liquid biopsy samples to ensure consistent and reliable results. Future research aims to address these challenges by refining techniques, improving signal detection, and integrating multi-omic data to enhance the accuracy and clinical utility of liquid biopsies.