K.V. Kitaeva*, A.A. Rizvanov**, V.V. Solovyeva***
Kazan Federal University, Kazan, 420008 Russia
E-mail: *olleth@mail.ru, **Albert.Rizvanov@kpfu.ru, ***solovyovavv@gmail.com
Received May 6, 2020
ORIGINAL ARTICLE
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DOI: 10.26907/2542-064X.2021.2.155-176
For citation: Kitaeva K.V., Rizvanov A.A., Solovyeva V.V. Modern methods of preclinical anticancer drug screening using test systems based on cell cultures. Uchenye Zapiski Kazanskogo Universiteta. Seriya Estestvennye Nauki, 2021, vol. 163, no. 2, pp. 155–176. doi: 10.26907/2542-064X.2021.2.155-176. (In Russian)
Abstract
Preclinical screening of medicinal drugs for novel anti-cancer treatments faces a problem of a rational approach to primary screening of substances with antitumor activity. Low correlation between in vitro and in vivo studies with clinical trials remains a serious issue. Choosing the right tumor model at the in vitro testing stage reduces the financial and time costs of finding and testing promising antitumor agents. In the light of the growing prevalence of cancer, it is urgently important to develop new approaches to screening of anticancer drugs, as well as to increase the pace of creation, development, and testing of new antitumor agents. Although the pharmaceutical industry uses mainly two-dimensional in vitro models, the field of preclinical screening needs more complex models, such as three-dimensional models, microfluidic systems, Boyden chamber, and models created using three-dimensional bioprinting. This review describes the above in vitro tumor models, including their use in research and features, in order to help researchers and clinicians from various fields of pharmacy, preclinical studies, and cell biology understand their prospects for screening potential antitumor drugs.
Keywords: antitumor drug screening, in vitro tumor model, two-dimensional cultures, three-dimensional cultures, microfluidic systems, Boyden chamber, tumor microenvironment, 3D bioprinting
Acknowledgments. The work is performed according to the Russian Government Program of Competitive Growth of Kazan Federal University and supported by the Russian Foundation for Basic Research (project no. 17-00-00263).
Figure Captions
Fig. 1. Test systems for anticancer drug screening: a) 2D cultures: 1 – monolayer of tumor cells, 2 – co-culture of tumor and stromal cells; b) 3D models of multicellular spheroids: 1 – spheroids consisting of tumor cells, 2 – tumor stroma model based on co-cultivation of several types of cells using the extracellular matrix model, 3 – spheroids created by the method of hanging drops; c) Boyden chamber for analysis of cell migration: cells with high invasive potential pass through a porous semipermeable membrane; d) microfluidic system for assessing the invasive potential of tumor cells: a mixture of hydrogel and cells is placed in the central channel, medium containing/devoid of factors (depending on the purpose of the experiment) placed in the lateral channels; e) tumor models created using bioprinting: 1 – layer of tumor cells between the layers of stromal cells, 2 – spheroids consisting of tumor cells, 3 – spheroids simulating tumor stroma and consisting of tumor cells mixed with stromal cells, 4 – glioma model embedded in the 3D-printed brain containing glioma cells and macrophages.
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