Decoding ctDNA: biological insights for accurate clinical interpretation

Circulating tumor DNA (ctDNA) is a key component of liquid biopsy and has emerged as one of the most promising biomarkers. However, the clinical value of ctDNA depends directly on the biological mechanisms that govern its release and persistence within the circulation. In this review, we provide an overview of the current understanding of ctDNA biology and its clinical implications. We describe the mechanisms of ctDNA shedding and clearance, as well as the factors that influence its dynamic balance. We discuss the role of ctDNA as a tumor biomarker, but also the hypothesis that ctDNA may also play an active role in tumor progression. A better understanding of these mechanisms is essential for accurately interpreting ctDNA analyses, optimizing their clinical use, and facilitating their integration into personalized cancer patient management.