The main sources of circulating cell-free DNA: Apoptosis, necrosis and active secretion

Cell-free DNA (cfDNA) as an emerging biomarker with huge potential for clinical application, especially in the field of liquid biopsy. The field is now in a critical transitional period in which cfDNA-based analysis is developing rapidly. No doubt learning more about the biological knowledge of cfDNA is beneficial to catalyze this transformation process. Therefore, in this review we have summarized the characteristics of cfDNA, including its structure and origin of tissues, in order to provide researchers with a more holistic insight of cfDNA. Subsequently, we focused on the pathways that cfDNA releases from cells, such as apoptosis, necrosis, and active secretion. Additionally, the clearance of cfDNA derived from both cellular death and active secretion in the physiological environment is also discussed. Finally, we have mentioned the link between cfDNA active secretion and tumor microenvironment.