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Updated: Jun 21, 2025
A Standardized Liquid Biopsy Preanalytical Protocol for Downstream Circulating-Free DNA Applications
Published on: September 16, 2022
Decoding the Dynamics of Circulating Tumor DNA in Liquid Biopsies
Khadija Turabi1,2, Kelsey Klute2,3, Prakash Radhakrishnan1,2
1Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Abstract:
Circulating tumor DNA (ctDNA), a fragment of tumor DNA found in the bloodstream, has emerged as a revolutionary tool in cancer management. This review delves into the biology of ctDNA, examining release mechanisms, including necrosis, apoptosis, and active secretion, all of which offer information about the state and nature of the tumor. Comprehensive DNA profiling has been enabled by methods such as whole genome sequencing and methylation analysis. The low abundance of the ctDNA fraction makes alternative techniques, such as digital PCR and targeted next-generation exome sequencing, more valuable and accurate for mutation profiling and detection. There are numerous clinical applications for ctDNA analysis, including non-invasive liquid biopsies for minimal residual disease monitoring to detect cancer recurrence, personalized medicine by mutation profiling for targeted therapy identification, early cancer detection, and real-time evaluation of therapeutic response. Integrating ctDNA analysis into routine clinical practice creates promising avenues for successful and personalized cancer care, from diagnosis to treatment and follow-up.
Insights
Circulating tumor DNA (ctDNA) analysis offers a non-invasive approach to cancer management. This technology aids in early detection, personalized medicine, and monitoring treatment response, transforming cancer care.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circulating tumor DNA (ctDNA) is DNA released from tumors into the bloodstream.
- Understanding ctDNA release mechanisms (necrosis, apoptosis, active secretion) provides insights into tumor biology.
- ctDNA analysis is a rapidly advancing field in oncology.
Purpose of the Study:
- To review the biology and clinical applications of ctDNA.
- To highlight methods for ctDNA detection and profiling.
- To discuss the potential of ctDNA in personalized cancer care.
Main Methods:
- Review of literature on ctDNA biology, detection methods, and clinical applications.
- Discussion of DNA profiling techniques including whole genome sequencing, methylation analysis, digital PCR, and targeted next-generation exome sequencing.
- Synthesis of current knowledge on ctDNA's role in cancer management.
Main Results:
- ctDNA analysis enables comprehensive DNA profiling.
- Digital PCR and targeted next-generation exome sequencing enhance mutation detection accuracy due to ctDNA's low abundance.
- Clinical applications include minimal residual disease monitoring, personalized therapy selection, early cancer detection, and treatment response evaluation.
Conclusions:
- ctDNA analysis is a powerful tool for non-invasive cancer management.
- Integrating ctDNA into clinical practice promises improved personalized cancer care from diagnosis through follow-up.
- Further research and clinical integration of ctDNA hold significant potential for advancing oncology.
