Circulating tumor DNA, or ctDNA, consists of small, fragmented pieces of DNA that are released by cancer cells into the bloodstream. These fragments carry the specific genetic and epigenetic alterations of the tumor they came from, making them powerful biomarkers. The presence of ctDNA in the blood provides a real-time snapshot of the cancer’s genetic landscape. This information is accessible through a simple blood draw, offering a non-invasive window into the tumor’s biology to help detect, monitor, and treat various types of cancer.
The Origin and Detection of ctDNA
Circulating tumor DNA originates from tumor cells. As tumors expand, some cells die through a programmed process called apoptosis, while others die from a lack of nutrients and oxygen in a process called necrosis. When these cells die and break apart, their contents, including fragmented DNA, are shed into the circulation.
Living tumor cells can also actively secrete DNA into the bloodstream. These released DNA fragments are typically short, often less than 200 base pairs in length, which distinguishes them from DNA released by healthy cells. The amount of ctDNA in the blood can vary widely depending on the tumor type, its size, location, and the stage of the cancer.
Detecting these minute quantities of DNA is accomplished through a liquid biopsy. This process begins with a standard blood draw, and in the laboratory, advanced molecular techniques like next-generation sequencing (NGS) are used to analyze the plasma. These technologies can identify and quantify the rare ctDNA fragments among the much larger background of normal cell-free DNA.
Clinical Applications in Cancer Care
The analysis of ctDNA has several direct applications in managing patients with an active cancer diagnosis. One use is in early cancer detection. For certain cancer types, the presence of ctDNA in the blood may signal a tumor’s existence before it becomes large enough to cause symptoms or be found by conventional imaging tests.
A more established application is guiding the selection of targeted therapies. Many modern cancer treatments are designed to attack cells with specific genetic mutations. By sequencing the ctDNA, oncologists can identify the unique genetic profile of a patient’s tumor and match it to a specific targeted drug.
ctDNA levels can also be tracked over time to monitor a patient’s response to treatment. A successful therapy that is shrinking a tumor will lead to a corresponding decrease in the amount of ctDNA, while stable or rising levels may indicate that the treatment is not working effectively.
Monitoring for Cancer Recurrence
One of the most powerful uses of ctDNA testing is in monitoring for cancer recurrence after a patient has completed their primary treatment, such as surgery or chemotherapy. Following these treatments, a small number of cancer cells can sometimes remain in the body. This state is known as Minimal Residual Disease (MRD), and these cells are too few to be detected by standard imaging scans like CT or PET scans.
These residual cells, however, continue to shed DNA into the bloodstream. ctDNA analysis is sensitive enough to detect these microscopic traces of the cancer long before it would become clinically apparent. A positive ctDNA test in a patient believed to be in remission can be the earliest sign that the cancer is returning.
This molecular signal can precede evidence of recurrence on imaging scans by several months or even longer. Detecting a recurrence at the MRD level provides a valuable window for intervention. It allows doctors to restart treatment at a much earlier stage, when the burden of cancer cells is still very low.
Comparison to Traditional Tissue Biopsies
The standard method for diagnosing and analyzing cancer has long been the tissue biopsy, which involves surgically removing a piece of the tumor for examination. While it remains the gold standard for initial diagnosis, it has limitations. A tissue biopsy is an invasive procedure that can carry risks, such as pain, bleeding, or infection.
It also provides a genetic snapshot from only one specific location of the tumor, which may not represent the full genetic diversity of the entire cancer or capture new mutations that arise as the cancer grows or adapts to treatment. Repeating a tissue biopsy to track changes in the tumor over time can be difficult, painful, and sometimes not feasible due to the tumor’s location.
A liquid biopsy for ctDNA offers a different approach. As a simple blood test, it is minimally invasive and can be performed repeatedly with minimal risk or discomfort to the patient. This allows for continuous monitoring of the tumor’s genetic makeup throughout the course of treatment. Because ctDNA is shed from cancer cells throughout the body, a liquid biopsy can provide a more comprehensive genetic profile of the entire cancer, including its metastases, overcoming the issue of tumor heterogeneity.