Minimal Residual Disease (MRD) in liquid biopsy (Part II)
In our previous article, we explored the importance of minimal residual disease (MRD) in cancer treatment, highlighting its role in predicting relapse and guiding personalized care. In this follow-up, we will delve into the methods used to measure MRD, the significance of MRD positivity and negativity, and how circulating tumor DNA (ctDNA) is revolutionizing MRD detection with its non-invasive and highly sensitive approach.
How is MRD Measured?
Measuring MRD requires highly sensitive tests capable of detecting one cancer cell among hundreds of thousands or even millions of healthy cells. Here are the primary methods:
- Flow Cytometry: This method uses fluorescent markers to detect and count cancer cells in a blood or bone marrow sample. It is especially effective in hematologic cancers (like leukemia) and is one of the most widely used MRD detection methods.
- Polymerase Chain Reaction (PCR): PCR detects specific DNA sequences unique to cancer cells, allowing it to pick out minuscule amounts of these cells in the bloodstream. This test is highly sensitive and can detect very low levels of MRD.
- Next-Generation Sequencing (NGS): NGS offers ultra-sensitive detection by deeply sequencing the cancer cells’ genetic profile. It is effective even in solid tumors and can identify MRD at levels as low as one cancer cell in a million normal cells.
MRD Positivity vs. MRD Negativity: What Does It Mean?
When a patient is tested for MRD, the result indicates whether any residual cancer cells remain in their body after treatment. A positive result, known as “MRD positivity,” means that small amounts of cancer cells are still detectable. This can suggest a higher risk of relapse, as these lingering cells have the potential to grow and cause the cancer to return.
On the other hand, “MRD negativity” is an encouraging sign. In this case, even the most sensitive tests fail to detect any residual cancer cells. For patients with blood cancers, achieving MRD negativity is an important milestone, as studies show it’s linked to longer periods of remission and improved survival rates. Essentially, MRD negativity offers a sense of reassurance that the treatment has been highly effective—though, of course, ongoing monitoring remains essential.
How Does ctDNA Contribute to MRD Determination?
Circulating tumor DNA (ctDNA) consists of DNA fragments shed into the bloodstream by cancer cells, either actively or through cell death. This DNA can be analyzed through a non-invasive blood test known as a “liquid biopsy,” which helps physicians detect residual cancer cells after treatment. Unlike traditional methods that require bone marrow or tissue samples, ctDNA testing is less invasive, easily repeatable, and particularly effective for solid tumors. With its ability to reveal even trace amounts of cancer-related DNA, ctDNA is crucial in identifying MRD. It provides a real-time, sensitive, and patient-friendly approach to tracking cancer presence, making it indispensable in personalized cancer care. Liqomics offers LymphoVista, a ctDNA-based MRD test for lymphomas with extremely high sensitivity and specificity and MRD monitoring solutions for other cancers. Learn more here and contact us now to learn more about us and what we can offer.
In summary
Minimal Residual Disease (MRD) refers to the tiny number of cancer cells that might persist after treatment. An “MRD-positive” result means some cancer cells remain, while “MRD-negative” indicates no detectable disease, which is often associated with longer remission and improved survival. MRD testing can guide further treatment, help monitor remission, and may even detect early relapse. Techniques like flow cytometry, PCR, and next-generation sequencing (NGS) are commonly used, each with high sensitivity to detect cancer cells among healthy cells. For many blood cancers, including leukemia, lymphoma, and myeloma, MRD testing offers a vital tool to personalize treatment, assess relapse risk, and improve outcomes.
Author: Lisa Baum, Bioinformatician and Data Scientist, Liqomics
