ctDNA and Cancer Diagnostics

By Priyanka Varma


Feb. 22nd, 2022

“ctDNA” (circulating tumor DNA) is the tumor-derived fraction of “cfDNA” (cell free DNA). It is a cancer biomarker utilized in cancer diagnostics among other applications, by liquid biopsy.  It is shed by tumor cells in peripheral blood and other bodily fluids [1]. ctDNA is being researched to be used as a diagnostic marker in several cancers including, lung cancer, colorectal cancer, prostate cancer, advanced adenomas,  immuno oncology, among others [2].

The clinical applications of ctDNA relies on mutation detection in plasma or serum of cancer patients, for the purpose of early cancer detection, to determine the tissue of origin, prognosis, to monitor response, or detect minimal residual disease. With the advent of precision medicine, it has been widely researched and benefited from using Next Generation Sequencing (NGS) technologies to improve its rate of detection. The amount of ctDNA is positively correlated to the volume of tumor and its rate of proliferation [3, 4]. The concentration of ctDNA is lesser in early stage cancer patients as compared to later stage cancer patients [2].

Apart from being non-invasive, quick and easy to perform, shorter turnaround times ctDNA obtained via liquid biopsy also offers an advantage of providing access to the cancer genome and information on intra and extra heterogeneity of the tumor, thereby avoiding the necessity of a potential invasive biopsy [3]. These broader approaches using NGS or mass spectrometry based PCR assist in whole genome typing would eventually help understand tumor heterogeneity, response to treatment, and identify potential new mutations [4].

The limitations of ctDNA as a diagnostic biomarker lies in its very low concentration in body fluid compared to cfDNA, requiring for the diagnostic test to have a very high sensitivity and specificity to accurately detect its presence, apart from the expense associated with comprehensive panels [3, 4].


  1. Stadler JC, Belloum Y, Deitert B, Sementsov M, Heidrich I, Gebhardt C, Keller L, Pantel K. Current and Future Clinical Applications of ctDNA in Immuno-Oncology. Cancer Res. 2022 Feb 1;82(3):349-358. doi: 10.1158/0008-5472.CAN-21-1718. Epub 2021 Nov 23. PMID: 34815256.
  2. Chen M, Zhao H. Next-generation sequencing in liquid biopsy: cancer screening and early detection. Hum Genomics. 2019 Aug 1;13(1):34. doi: 10.1186/s40246-019-0220-8. PMID: 31370908; PMCID: PMC6669976.
  3. Gilson P. Enrichment and Analysis of ctDNA. Recent Results Cancer Res. 2020;215:181-211. doi: 10.1007/978-3-030-26439-0_10. PMID: 31605230.
  4. Keller L, Belloum Y, Wikman H, Pantel K. Clinical relevance of blood-based ctDNA analysis: mutation detection and beyond. Br J Cancer. 2021;124(2):345-358. doi:10.1038/s41416-020-01047-5

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