Perspectives for the analysis of circulating tumor DNA in clinical oncology: achievements and unresolved issues

Abstract

The efforts to detect specific tumor-associated changes in blood and other biological fluids are by no means new. However, only the development of the most precise modifications of DNA analysis provided real opportunity to monitor tumor behavior in “real time” manner. Two directions should be distinguished within this field of modern oncology: 1) the early detection of cancer in apparently healthy individuals; 2) the use of liquid biopsy in patients with confirmed cancer diagnosis for a broad range of applications, such as the early diagnosis of recurrence or monitoring the treatment efficacy.
 It should be stated, that the first direction of the research has not yet led to the results suitable for implementation in real world practice. Nevertheless, there are staggering technological advances in the analytical performance of NGS-based methods, which are applied to this task. The emerging non-standard approaches, involving the use of recently discovered peculiarities of the ctDNA fragmentation in plasma, or the complex approaches, utilizing a number of diverse methods simultaneously, are of great interest. The second, less ambitious direction of liquid biopsy studies is much closer to clinical use. This approach has already been widely used for such an actual issue, as the early non-invasive T790M detection in plasma of metastatic lung cancer patients, undergoing anti-EGFR therapy. Aside from the practical advances, the studies of various aspects of liquid biopsy provide all sorts of invaluable scientific information, for example regarding the precise timing patterns of the emergence of the resistance to anticancer drugs and the dynamics of its regression after changing of therapy regimen.