ART OF MEDICINE 2017
LIQUID BIOPSY: PERSPECTIVES OF APPLICATION IN ONCOLOGY (LITERATURE REVIEW)
І.О. Vynnychenko, A.O. Pryvalova, O.M. Smorodska, O.І. Vynnychenko,Y.V. Moskalenko
Abstract. Nowadays liquid biopsy is under the focus of attention due to its clinical implications for personalized medicine. This diagnostic method focuses on detection and analysis of blood biomarkers such as circulating tumor cells (CTC), cell-free circulating tumor DNA (ctDNA), circulating RNA and exosomes that are released from primary tumors and their metastatic focuses. Benefits of liquid biopsy over classic tissue biopsy are obvious. Non-invasiveness and heterogeneity of the method makes it possible to detect all variants of tumor cells types. Detection of different tumor cells types allow oncologists to approach the personalized treatment.
Calculation of CTC can be used as a prognostic factor that allows to determinate survival rate without progression and overall survival, especially in patients with non-small cell lung cancer, breast cancer, colorectal cancer, and prostate cancer. Different techniques have been used to calculate number of CTC. Some techniques are based on biological properties of cells, while others - on physical properties. It has been shown that the number of metastases depends on the amount of CTC. It is also known that the CTC could also be released into the bloodstream from secondary metastatic focuses, even if resection of the primary tumor was made many years ago.
ctDNA are DNA fragments of lysed tumor cells that could be found in systemic circulation. Due to the low number of such fragments in the circulating blood, there are some difficulties in the analysis. The latest elaborations in molecular technologies made possible to achieve necessary sensitivity and specificity in detecting of ctDNA in low rates. In principle, methods for detecting ctDNA can be divided into targeted approaches that aim to detect mutations in a set of predefined genes or untargeted approaches that aim to screen the genome and discover new genomic aberrations.
A small but very promising section of the liquid biopsy is the definition of tumor circulating RNA. Prospect of its widespread use is associated with ability to detect them in most biological fluids, such as plasma, serum, cerebrospinal fluid, saliva and urine, which could be referred to its’ significant advantage. The main problems for its widespread use are lack of standardization as well as high dependence of obtained results on the conditions that preceded the analysis. In particular temperature, preservatives that are used, patient's diet, lifestyle and received drugs could affect obtained results.
Analyses of CTCs and ctDNA have paved new diagnostic ways of liquid biopsy. Key areas of clinical applications of liquid biopsy are cancer detection, prediction of prognosis in patients with curable disease, monitoring systemic therapies and stratification of patients based on the detection of therapeutic targets or resistant mechanisms; but to what extent they might replace tissue biopsy in the future is still the subject to be discussed.
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