Scientists can now find tiny fragments of DNA, shed by tumors, circulating freely in a patient’s bloodstream. This innovative approach is known as circulating tumor DNA (ctDNA) testing, often referred to as a “liquid biopsy.” It represents a significant advancement in cancer detection and management, offering a less invasive way to gather information about a tumor without traditional tissue sampling.
Understanding Circulating Tumor DNA
Circulating tumor DNA (ctDNA) represents fragments of genetic material released into the bloodstream by cancerous cells when they die and break apart. While the blood contains a general pool of cell-free DNA (cfDNA) from normal cells, ctDNA is a specific subset distinguished by its cancer-specific genetic alterations. Think of cfDNA as background noise, with ctDNA being the distinct voice from the tumor. The presence and characteristics of these tumor-derived fragments offer unique insights into the cancer’s genetic makeup.
The Liquid Biopsy Procedure
A liquid biopsy begins with a simple and routine blood draw, much like any other standard blood test. Once collected, the sample is sent to a specialized laboratory. There, plasma is separated from blood cells.
Following plasma isolation, sophisticated molecular techniques extract and purify cell-free DNA, including ctDNA. This DNA is then subjected to advanced genomic analysis, most commonly using Next-Generation Sequencing (NGS). NGS allows researchers to rapidly read millions of DNA sequences, searching for specific genetic mutations or alterations known to be associated with cancer.
Applications in Cancer Management
ctDNA testing has several applications in cancer management.
It monitors treatment effectiveness. By regularly measuring ctDNA levels, doctors can observe if the amount of tumor DNA in the blood decreases (suggesting effective treatment) or increases (indicating potential progression or resistance). This provides an early indicator of treatment response, sometimes even before changes are visible on traditional imaging scans.
The test also detects minimal residual disease (MRD) after surgery or other primary treatments. Even if scans show no visible cancer, tiny clusters of remaining cancer cells can shed ctDNA. Identifying MRD through a blood test can help determine which patients might benefit from additional therapy to prevent recurrence.
ctDNA testing guides the selection of targeted therapies. Many modern cancer drugs attack cells with specific genetic mutations. By analyzing ctDNA, doctors can identify these mutations, such as EGFR mutations in lung cancer or BRAF mutations in melanoma, allowing for precise drug selection tailored to the patient’s cancer.
The test can also identify when a tumor develops resistance to a previously effective treatment. As tumors evolve, they can acquire new mutations that make them unresponsive. ctDNA testing can detect these new resistance mutations, like the T790M mutation in EGFR-mutated lung cancer, often before clinical symptoms appear. This allows clinicians to adjust treatment strategies promptly.
Test Performance and Emerging Possibilities
The accuracy of ctDNA testing is influenced by factors like tumor type and size. Some tumors, such as colorectal or lung cancers, tend to shed more ctDNA, making them easier to detect, while others, like certain brain tumors, may shed less. Larger tumors also generally release more ctDNA into the bloodstream.
Research is expanding ctDNA testing for multi-cancer early detection (MCED) screening in individuals without a known cancer diagnosis. This involves developing highly sensitive tests to detect ctDNA from various cancer types at early stages. The goal is to identify cancer when it is most treatable, improving patient outcomes.