METHODOLOGICAL APPROACHES TO THE DETERMINATION OF CHEMORESISTANCE OF HUMAN CANCER CELLS TO ANTI-CANCER DRUGS

Abstract

The purpose of the study was to analyze the existing methodological approaches to the experimental testing of resistance to chemotherapy and assess the prospects for their further application.Material and Methods. We analyzed publications regarding the experimental testing of tumor resistance to chemotherapy available in the databases, such as SciVerse Scopus (748), PubMed (1727), Web of Science (1025), RSCI (125). To obtain fulltext publications, the electronic resources of Research Gate, RSCI, CyberLenink were used. Forty-two modern publications (2012–19) including 18 articles of the founders of the methods analyzed in the review were cited.Results. The review discusses the characteristics of the main methods for assessing the resistance / sensitivity of tumor cells obtained from biopsy / surgical specimens to various chemotherapy drugs in vitro in monolayer and suspension cultures, in the form of spheroids, histo and organocultures, as well as in vivo xenografts of tumors in immunodeficient mice. During testing, the proliferative and metabolic activities as well as the level of cell death were considered as the main evaluated characteristics of tumor cells. The main indicators were the intensity of DNA synthesis, the level of protein or ATP in the cell, the activity of NADH-dehydrogenases, the level of apoptosis, and the integrity of cell structures. The advantages and disadvantages of the described methods, as well as the prospects for their further application were discussed.Conclusion. Over the past half century of using the experimental testing of tumor cell resistance in order to personalize chemotherapeutic treatment, the evolution of methodological approaches was based on the increase in their safety and sensitivity through the use of fluorescent compounds. The general vector for improving experiments on the personalization of tumor chemotherapy is aimed at approximating the experimental conditions to the processes occurring in the human body. Each of these methods has its own range of predictive power and, if used properly, can provide a useful guide for treatment.

Keywords

• tumor
• cell culture
• histoculture
• spheroids
• xenografts
• cytostatics
• targeted drugs
• resistance