What is circulating tumor DNA and how is it used to diagnose and manage cancer?

Circulating tumor DNA (ctDNA) is found in the bloodstream and refers to DNA that comes from cancerous cells and tumors. Most DNA is inside a cell’s nucleus. As a tumor grows, cells die and are replaced by new ones. The dead cells get broken down and their contents , including DNA, are released into the bloodstream. ctDNA are small pieces of DNA, usually comprising fewer than 200 building blocks (nucleotides) in length.
The quantity of ctDNA varies among individuals and depends on the type of tumor, its location, and for cancerous tumors, the cancer stage. Detection of ctDNA can be helpful in the following cases:
• Detecting and diagnosing a tumor. Because tumor DNA has acquired multiple genetic mutations , leading to tumor development, ctDNA is not an exact match to the individual’s DNA. Finding DNA with genetic differences aids in tumor detection. Diagnosing the type of tumor using ctDNA can reduce the need for getting a sample of the tumor tissue (tumor biopsy), which can be challenging when a tumor is difficult to access, such as a tumor in the brain or lung.
• Guiding tumor-specific treatment. Analyzing the genome of tumor cells using ctDNA can help doctors determine which treatment will be most effective. Currently, however, approval from the U.S. Food and Drug Administration for ctDNA testing to personalize cancer treatment is limited.
• Monitoring treatment. A decrease in the quantity of ctDNA suggests the tumor is shrinking and treatment is successful.
• Monitoring periods with no symptoms (remission of cancer). A lack of ctDNA in the bloodstream indicates that the cancer has not returned.

Scientists have discovered that dying tumor cells release small pieces of their DNA into the bloodstream. These pieces are called cell-free circulating tumor DNA (ctDNA).