Liquid Biopsy and ctDNA - A New Era in Cancer Testing

If you're facing cancer, you've likely experienced the anxiety of waiting for test results or undergoing invasive procedures. The good news is that medical science is evolving rapidly, and one of the most exciting advances is liquid biopsy - a simpler, less invasive way to detect and monitor cancer using just a blood sample.

What is liquid biopsy?

Liquid biopsy is a minimally invasive approach to cancer testing that analyzes markers released by tumors into your bloodstream and other body fluids. Unlike traditional tissue biopsy, which requires surgical removal of a piece of tumor tissue, liquid biopsy typically uses a simple blood draw - similar to routine blood work.

Think of it as catching tiny clues that cancer cells leave behind as they naturally die or shed material into your bloodstream. These clues can tell your medical team important information about your cancer without the need for surgery or more invasive procedures.

How does liquid biopsy work?

During a liquid biopsy, a healthcare provider draws a small blood sample from your arm. This sample is then sent to a specialized laboratory where scientists use advanced molecular techniques to detect and analyze:

Circulating tumor DNA (ctDNA): Fragments of DNA released by cancer cells
Circulating tumor cells (CTCs): Actual cancer cells traveling in the bloodstream
Extracellular vesicles: Small packages that carry tumor-related proteins and genetic material

The most commonly analyzed component is ctDNA, which has proven to be particularly valuable for cancer monitoring.

Understanding ctDNA (circulating tumor DNA)

Circulating tumor DNA (ctDNA) refers to small fragments of DNA shed from cancer cells as they die or turn over. According to research published in Nature, these fragments enter the bloodstream and can be detected using sophisticated molecular techniques like PCR and next-generation sequencing.

Here's what makes ctDNA special:

Cancer-specific mutations: Since tumor cells carry specific genetic mutations different from healthy cells, ctDNA provides a snapshot of your cancer's genetic makeup at any given moment
Real-time information: ctDNA has a short half-life in the blood, meaning changes in levels reflect what's happening with your tumor right now
Dynamic tracking: By testing your blood over time, doctors can see how your cancer is responding to treatment

Where does ctDNA come from?

ctDNA is released into the blood primarily when cancer cells die (through natural cell death or treatment), but also through active secretion. It's a subfraction of cell-free DNA, which is released by both tumor and normal cells. Tumor-derived ctDNA is typically shorter, which helps distinguish it from normal DNA.

How is liquid biopsy used in cancer care?

The Cleveland Clinic explains that liquid biopsy has several important applications in modern cancer care:

1. Cancer detection and diagnosis

Liquid biopsy can help identify the presence of cancer, especially when traditional biopsies are difficult, risky, or not feasible due to:

Tumor location that's hard to reach
Patient health conditions that make surgery risky
Need for repeat testing without additional invasive procedures

2. Genetic profiling for personalized treatment

By analyzing ctDNA, doctors can detect:

Specific tumor mutations
Gene fusions and copy number changes
Actionable mutations that may respond to targeted therapies

This information helps your medical team choose the most effective treatment for your specific type of cancer.

3. Monitoring treatment response

By testing your blood regularly during treatment, your doctors can:

See if ctDNA levels are dropping (indicating treatment is working)
Detect rising levels early (which may signal treatment resistance)
Make informed decisions about continuing or changing therapy

This is much faster and less invasive than waiting for imaging scans to show changes.

4. Detecting minimal residual disease (MRD)

After surgery or therapy, small amounts of cancer may remain that are too tiny to see on scans. Studies show that ctDNA testing can detect these microscopic traces of disease, allowing for earlier intervention before cancer returns.

5. Tracking tumor evolution

Cancer cells can change over time, especially in response to treatment. Liquid biopsy allows doctors to track these genetic changes and adjust treatment strategies as resistance mutations emerge.

The difference between ctDNA and traditional tumor markers

You may be familiar with traditional tumor markers like CEA (Carcinoembryonic Antigen) or CA19-9, which are proteins often measured in blood tests for certain cancers. While both ctDNA and traditional markers are detected through blood tests, they differ significantly:

Traditional tumor markers (CEA, CA19-9)

What they measure: Proteins produced by cancer cells or by the body in response to cancer

Strengths:

Easy and inexpensive to test
Widely available
Useful for general monitoring

Limitations:

Not always cancer-specific (can be elevated in non-cancerous conditions like inflammation or liver disease)
Not all cancer patients have elevated markers
Less sensitive for detecting small amounts of disease
Don't provide information about specific cancer mutations

ctDNA testing

What it measures: DNA fragments with cancer-specific genetic mutations

Strengths:

High specificity (mutations are unique to cancer)
Can detect very small amounts of disease
Provides genetic information to guide targeted therapy
Changes more quickly reflect current tumor activity
Studies show earlier detection of recurrence compared to traditional markers

Limitations:

More expensive and complex
Less widely available
Requires specialized laboratories
May not detect disease in very early stages

In practice: Many doctors use both types of tests together, along with imaging and physical examinations, to get the most complete picture of your cancer.

Liquid biopsy around the world

The adoption of liquid biopsy technology is expanding globally, though availability and clinical use vary by country and healthcare system.

United States

In the United States, ctDNA-based liquid biopsies are increasingly integrated into cancer care. The FDA has approved several liquid biopsy platforms, including:

Guardant360 CDx: Used for lung cancer and breast cancer to identify specific mutations
FoundationOne Liquid CDx: A companion diagnostic for multiple cancer types

In November 2024, the FDA released guidance clarifying the use of ctDNA as a biomarker in cancer drug development and clinical trials. The agency has approved tests particularly for lung, breast, and colorectal cancers, where they help doctors select targeted therapies and monitor treatment response.

Europe

European countries have been actively embracing liquid biopsy technology through large research programs and clinical trials. The European regulatory agencies have been evaluating ctDNA tests, with several approved for clinical use in conjunction with multi-center studies.

Major initiatives include:

Large-scale clinical validation studies in colorectal cancer
Integration into national health systems for treatment monitoring
Research collaborations focused on early cancer detection

Asia

Asian countries, particularly Japan, have been at the forefront of liquid biopsy research and implementation. Studies like CIRCULATE-Japan and the GALAXY study have demonstrated the prognostic value of ctDNA in colorectal cancer and other tumor types.

Asian institutions are also developing highly sensitive ctDNA assays and advancing precision oncology through national liquid biopsy programs.

Global efforts for standardization

The International Society of Liquid Biopsy (ISLB) is working with researchers and clinicians worldwide to establish quality control standards and harmonize testing methodologies. This collaboration aims to ensure reliable and reproducible results across different laboratories and healthcare systems.

What to expect if your doctor orders a liquid biopsy

If your healthcare team recommends a liquid biopsy, here's what typically happens:

Blood draw: A nurse or phlebotomist will draw a small blood sample from your arm - just like routine blood work
Laboratory processing: The sample is sent to a specialized laboratory equipped with advanced genetic testing technology
Analysis time: Results typically take 1-2 weeks, depending on the test and laboratory
Result discussion: Your doctor will review the results with you and explain what they mean for your treatment plan

No special preparation is usually needed, and you can typically continue your normal activities immediately after the blood draw.

The future of liquid biopsy

Research in liquid biopsy is advancing rapidly. Scientists are working on:

Earlier detection: Developing tests that can catch cancer at its earliest, most treatable stages
Multi-cancer detection: Tests that can screen for multiple types of cancer from a single blood sample
Improved sensitivity: Making tests more accurate even when ctDNA levels are very low
Wider availability: Making liquid biopsy accessible to more patients worldwide

While liquid biopsy won't completely replace traditional biopsies or imaging in the near future, it's becoming an increasingly valuable tool in the cancer care toolkit.

Important reminders

While liquid biopsy is a powerful tool, it's important to remember:

Not all cancers shed enough ctDNA: Some tumors, especially very small or slow-growing ones, may not release detectable amounts of DNA into the blood
Negative doesn't always mean cancer-free: A negative liquid biopsy doesn't guarantee there's no cancer - your doctor will use multiple tests to monitor your condition
Always discuss with your doctor: Liquid biopsy results should always be interpreted by your healthcare team in the context of your overall clinical picture

"Liquid biopsy represents hope - hope for earlier detection, more personalized treatment, and better monitoring of how therapy is working. While the technology continues to evolve, it's already making a difference in cancer care today."

Taking control of your cancer journey

Understanding the tools available for detecting and monitoring cancer can help you feel more empowered in your treatment journey. If you're interested in liquid biopsy:

Your medical team is there to explain what each test means for your care
It's okay to ask questions - no question is too small or too simple
Use OncoSteps to help you prepare a list of questions for your next oncologist appointment
Inquire about which tests are available and covered by your insurance
Discuss how the results could impact your treatment decisions
Stay informed about new developments in this rapidly evolving field

Remember, you're not alone in this journey. Your healthcare team is there to guide you through each step, explain your options, and work with you to develop the best possible treatment plan.

You're not alone - we're here to support you every step of the way.