Circulating tumor DNA as a biomarker to detect minimal residual disease for colorectal and breast cancer

Abstract

Minimal residual disease (MRD) is a key contributor to cancer recurrence, often escaping detection by conventional imaging and biomarker techniques. Circulating tumor DNA (ctDNA), a component of cell-free DNA shed by tumor cells into the bloodstream, has emerged as a promising biomarker for the non-invasive detection and monitoring of MRD in solid tumors. This review critically examines current evidence on the application of ctDNA for MRD detection in colorectal cancer (CRC) and breast cancer, two of the most common malignancies worldwide. It compares ctDNA detection platforms, including digital droplet PCR (ddPCR) and next-generation sequencing (NGS), emphasizing differences in sensitivity, specificity, and clinical relevance. The review also discusses the use of tumor-informed versus untargeted ctDNA assays and highlights key biomarkers such as KRAS, BRAF, TP53, and PIK3CA. Although ctDNA holds substantial potential to enhance surveillance strategies, challenges such as assay variability and tumor heterogeneity must be addressed to enable broader clinical implementation.