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Updated: Apr 21, 2026
A Standardized Liquid Biopsy Preanalytical Protocol for Downstream Circulating-Free DNA Applications
Published on: September 16, 2022
Circulating tumor DNA as a liquid biopsy for cancer
Ellen Heitzer1, Peter Ulz2, Jochen B Geigl2
1Institute of Human Genetics, Medical University of Graz, Graz, Austria. ellen.heitzer@medunigraz.at.
Background:
Targeted therapies have markedly changed the treatment of cancer over the past 10 years. However, almost all tumors acquire resistance to systemic treatment as a result of tumor heterogeneity, clonal evolution, and selection. Although genotyping is the most currently used method for categorizing tumors for clinical decisions, tumor tissues provide only a snapshot, or are often difficult to obtain. To overcome these issues, methods are needed for a rapid, cost-effective, and noninvasive identification of biomarkers at various time points during the course of disease. Because cell-free circulating tumor DNA (ctDNA) is a potential surrogate for the entire tumor genome, the use of ctDNA as a liquid biopsy may help to obtain the genetic follow-up data that are urgently needed.
Content:
This review includes recent studies exploring the diagnostic, prognostic, and predictive potential of ctDNA as a liquid biopsy in cancer. In addition, it covers biological and technical aspects, including recent advances in the analytical sensitivity and accuracy of DNA analysis as well as hurdles that have to be overcome before implementation into clinical routine.
Summary:
Although the analysis of ctDNA is a promising area, and despite all efforts to develop suitable tools for a comprehensive analysis of tumor genomes from plasma DNA, the liquid biopsy is not yet routinely used as a clinical application. Harmonization of preanalytical and analytical procedures is needed to provide clinical standards to validate the liquid biopsy as a clinical biomarker in well-designed and sufficiently powered multicenter studies.
Insights
Liquid biopsy using cell-free circulating tumor DNA (ctDNA) offers a noninvasive method for cancer monitoring. Further standardization is needed to establish ctDNA as a routine clinical biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Targeted cancer therapies have advanced significantly, but tumor resistance remains a major challenge.
- Current tumor genotyping provides limited, static information and can be invasive.
- Tumor heterogeneity and clonal evolution necessitate dynamic monitoring of cancer progression.
Purpose of the Study:
- To review the diagnostic, prognostic, and predictive potential of cell-free circulating tumor DNA (ctDNA) as a liquid biopsy in cancer.
- To explore biological and technical aspects of ctDNA analysis.
- To identify hurdles for the clinical implementation of liquid biopsies.
Main Methods:
- Literature review of recent studies on ctDNA in cancer.
- Analysis of biological and technical advancements in ctDNA detection.
- Evaluation of challenges in translating ctDNA analysis to clinical practice.
Main Results:
- ctDNA shows promise as a noninvasive surrogate for tumor genotyping.
- Advances in DNA analysis enhance sensitivity and accuracy for ctDNA detection.
- Significant hurdles remain before routine clinical adoption of ctDNA liquid biopsies.
Conclusions:
- ctDNA liquid biopsy is a promising tool for cancer genetic follow-up.
- Standardization of preanalytical and analytical procedures is crucial.
- Well-designed multicenter studies are required to validate ctDNA as a clinical biomarker.
