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Updated: Jul 14, 2025
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Clinical application of circulating tumor DNA in metastatic cancers
Negin Raei1,2, Reza Safaralizadeh2, Saeid Latifi-Navid3
1Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
Introduction:
Advances in genomics have facilitated the application of cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) in phase II and phase III clinical trials. The various mutations of cfDNA/ctDNA have been correlated with clinical features. Advances in next-generation sequencing (NGS) and digital droplet PCR have paved the way for identifying cfDNA/ctDNA mutations.
Areas Covered:
Herein, the biology of ctDNA and its function in clinical application in metastasis, which may lead to improved clinical management of metastatic cancer patients, are comprehensively reviewed.
Expert Opinion:
Metastatic cancer ctDNA shows the greatest frequency of mutations in TP53, HER-2, KRAS, and EGFR genes (alteration frequency of > 50%). Therefore, identifying key mutations frequently present in metastatic cancers can help identify patients with pre-malignant tumors before cancer progression. Studying ctDNA can help determine the prognosis and select appropriate treatments for affected patients. Nevertheless, the obstacles to detecting and analyzing ctDNA should be addressed before translation into routine practice. Also, more clinical trials should be conducted to study the significance of ctDNA in commonly diagnosed malignancies. Given the recent advances in personalized anti-neoplastic treatments, further studies are needed to detect a panel of ctDNA and patient-specific ctDNA for various cancers.
Insights
Circulating tumor DNA (ctDNA) analysis aids in managing metastatic cancer by identifying key mutations like TP53 and KRAS. Further research is needed to overcome detection challenges and integrate ctDNA into routine clinical practice.
Area of Science:
- Genomics
- Molecular Oncology
- Cancer Biology
Background:
- Cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) are increasingly used in clinical trials.
- Advances in next-generation sequencing (NGS) and digital droplet PCR enable cfDNA/ctDNA mutation detection.
Purpose of the Study:
- To comprehensively review the biology of ctDNA.
- To discuss the clinical applications of ctDNA in managing metastatic cancer.
- To highlight the potential for improved clinical management of metastatic cancer patients.
Main Methods:
- Review of existing literature on ctDNA biology and clinical applications.
- Analysis of mutation frequencies in metastatic cancers.
- Discussion of challenges and future directions for ctDNA implementation.
Main Results:
- Metastatic cancer ctDNA frequently harbors mutations in TP53, HER-2, KRAS, and EGFR genes (>50% alteration frequency).
- Identifying these key mutations can help detect pre-malignant tumors and guide prognosis and treatment selection.
- Obstacles in ctDNA detection and analysis need to be addressed for routine clinical use.
Conclusions:
- ctDNA holds significant potential for personalized cancer treatment and improved patient management.
- Further clinical trials are essential to validate the significance of ctDNA in common malignancies.
- Development of ctDNA panels and patient-specific ctDNA detection is crucial for advancing personalized anti-neoplastic therapies.
