Life and death of circulating cell-free DNA

Cancer Biol Ther. 2019;20(8):1057-1067. doi: 10.1080/15384047.2019.1598759. Epub 2019 Apr 16.


Tumor-specific, circulating cell-free DNA in liquid biopsies is a promising source of biomarkers for minimally invasive serial monitoring of treatment responses in cancer management. We will review the current understanding of the origin of circulating cell-free DNA and different forms of DNA release (including various types of cell death and active secretion processes) and clearance routes. The dynamics of extracellular DNA in blood during therapy and the role of circulating DNA in pathophysiological processes (tumor-associated inflammation, NETosis, and pre-metastatic niche development) provide insights into the mechanisms that contribute to tumor development and metastases formation. Better knowledge of circulating tumor-specific cell-free DNA could facilitate the development of new therapeutic and diagnostic options for cancer management.

Keywords: Cell-free DNA; cancer; circulating tumor DNA; inflammation; liquid biopsy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / immunology
  • Cell Transformation, Neoplastic / metabolism
  • Cell-Free Nucleic Acids*
  • Circulating Tumor DNA*
  • DNA, Neoplasm*
  • Humans
  • Liquid Biopsy / methods
  • Neoplasms / blood
  • Neoplasms / diagnosis
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Organ Specificity


  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids
  • Circulating Tumor DNA
  • DNA, Neoplasm

Grant support

This work was supported by the Ministry of Science and Technology, Israel [Personalized Medicine Grant 2017-2020].