Epigenetic liquid biopsies for minimal residual disease, what’s around the corner?

Abstract

Liquid biopsy assays for minimal residual disease (MRD) are used to monitor and inform oncological treatment and predict the risk of relapse in cancer patients. To-date, most MRD assay development has focused on targeting somatic mutations. However, epigenetic changes are more frequent and universal than genetic alterations in cancer and circulating tumor DNA (ctDNA) retains much of these changes. Here, we review the epigenetic signals that can be used to detect MRD, including DNA methylation alterations and fragmentation patterns that differentiate ctDNA from noncancerous circulating cell-free DNA (ccfDNA). We then summarize the current state of MRD monitoring; highlight the advantages of epigenetics over genetics-based approaches; and discuss the emerging paradigm of assaying both genetic and epigenetic targets to monitor treatment response, detect disease recurrence, and inform adjuvant therapy.

Harnessing Minimal Residual Disease as a Predictor for Colorectal Cancer: Promising Horizons Amidst Challenges

“…Recognized as an innovative marker for MRD, DNA methylation has the advantage of not requiring complete sequencing of the tumor tissue genome. It can be used directly for blood testing, avoiding the risk of a false-positive from mutations originating in normal tissue, non-malignant conditions, or clonal hematopoiesis [53]. Research conducted in both France and China has presented findings on a two-gene and multi-gene methylation marker detection method for CRC blood samples, providing guidance for determining appropriate ACT strategies [37,48].…”