Improvements in genomic and molecular methods are expanding the range of potential applications for circulating tumour DNA (ctDNA), both in a research setting and as a 'liquid biopsy' for cancer management. Proof-of-principle studies have demonstrated the translational potential of ctDNA for prognostication, molecular profiling and monitoring. The field is now in an exciting transitional period in which ctDNA analysis is beginning to be applied clinically, although there is still much to learn about the biology of cell-free DNA. This is an opportune time to appraise potential approaches to ctDNA analysis, and to consider their applications in personalized oncology and in cancer research.

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Liquid biopsies come of age: towards implementation of circulating tumour DNA

The emerging role of cell-free DNA as a molecular marker for cancer management.

Over the last decades, the concept of precision medicine has dramatically renewed the field of medical oncology; the introduction of patient-tailored therapies has significantly improved all measur...

https://journals.sagepub.com/doi/pdf/10.1177/1758835918794630

Liquid biopsy of cancer: a multimodal diagnostic tool in clinical oncology

Circulating tumor DNA (ctDNA) is a component of cell-free DNA that is shed by malignant tumors into the bloodstream and other bodily fluids. Levels of ctDNA are typically low, particularly in patients with localized disease, requiring highly sophisticated methods for detection and quantification. Multiple liquid biopsy methods have been developed for ctDNA analysis in solid tumor malignancies and are now enabling detection and assessment of earlier stages of disease, post-treatment molecular residual disease (MRD), resistance to targeted systemic therapy, and tumor mutational burden. Understanding ctDNA biology, mechanisms of release, and clearance and size characteristics, in conjunction with the application of molecular barcoding and targeted error correction, have increased the sensitivity and specificity of ctDNA detection techniques. Combinatorial approaches including integration of ctDNA data with circulating protein biomarkers may further improve assay sensitivity and broaden the scope of ctDNA applications. Circulating viral DNA may be utilized to monitor disease in some virally induced malignancies. In spite of increasingly accurate methods of ctDNA detection, results need to be interpreted with caution given that somatic mosaicisms such as clonal hematopoiesis of indeterminate potential (CHIP) may give rise to genetic variants in the bloodstream unrelated to solid tumors, and the limited concordance observed between different commercial platforms. Overall, highly precise ctDNA detection and quantification methods have the potential to transform clinical practice via non-invasive monitoring of solid tumor malignancies, residual disease detection at earlier timepoints than standard clinical and/or imaging surveillance, and treatment personalization based on real-time assessment of the tumor genomic landscape.

/pdf/detection-of-solid-tumor-molecular-residual-disease-mrd-20zr7nhxxh.pdf

Detection of Solid Tumor Molecular Residual Disease (MRD) Using Circulating Tumor DNA (ctDNA).

Circulating cell-free DNA is considered as one of the major breakthroughs in the field of innovative diagnosis, used as a liquid biopsy. The kinetic parameters of a biomarker are mandatory to assess its usefulness as a diagnostic tool. Obtaining precise mathematical values for the kinetic parameters (e.g., half-life) is then crucial because it could be used for therapeutic monitoring as a prognostic factor. However, little is known about the intrinsic properties of circulating cell-free DNA, more especially, its kinetic properties within the organism. We summarized the basic principles that may affect the kinetics of circulating cell-free DNA within the organism in the light of biological and clinical evidence. We also meta-analyzed the reported data in the literature and the methodologies that have been used to study the kinetic parameters of human circulating cell-free DNA in vivo.

https://www.future-science.com/doi/pdf/10.4155/fsoa-2017-0140

Xiao Nan

Papers

Evaluation and comparison of in vitro degradation kinetics of DNA in serum, urine and saliva: A qualitative study.