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Tumor Organoids: The Era of Personalized Medicine

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Abstract

The strategies of future medicine are aimed to modernize and integrate quality approaches including early molecular-genetic profiling, identification of new therapeutic targets and adapting design for clinical trials, personalized drug screening (PDS) to help predict and individualize patient treatment regimens. In the past decade, organoid models have emerged as an innovative in vitro platform with the potential to realize the concept of patient-centered medicine. Organoids are spatially restricted three-dimensional clusters of cells ex vivo that self-organize into complex functional structures through genetically programmed determination, which is crucial for reconstructing the architecture of the primary tissue and organs. Currently, there are several strategies to create three-dimensional (3D) tumor systems using (i) surgically resected patient tissue (PDTOs, patient-derived tumor organoids) or (ii) single tumor cells circulating in the patient’s blood. Successful application of 3D tumor models obtained by co-culturing autologous tumor organoids (PDTOs) and peripheral blood lymphocytes have been demonstrated in a number of studies. Such models simulate a 3D tumor architecture in vivo and contain all cell types characteristic of this tissue, including immune system cells and stem cells. Components of the tumor microenvironment, such as fibroblasts and immune system cells, affect tumor growth and its drug resistance. In this review, we analyzed the evolution of tumor models from two-dimensional (2D) cell cultures and laboratory animals to 3D tissue-specific tumor organoids, their significance in identifying mechanisms of antitumor response and drug resistance, and use of these models in drug screening and development of precision methods in cancer treatment.

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Abbreviations

AdSC:

adult stem cell

CIN:

chromosomal instability

CTCs:

circulating tumor cells

CRISPR:

clustered regularly interspaced short palindromic repeats

CTLA-4:

cytotoxic T lymphocyte-associated antigen 4

EGFR:

epidermal growth factor receptor

ECM:

extracellular matrix

iPSC:

induced pluripotent stem cell

PDTO:

patient-derived tumor organoid

PDX:

patient-derived xenograft

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Acknowledgments

The authors are deeply thankful to O. A. Bezborodova (National Medical Radiology Research Center of the Ministry of Health of the Russian Federation, P. Hertsen Moscow Oncology Research Institute) for valuable comments in the process of review preparation.

Funding

This study was supported by the Russian Science Foundation (agreement no. 221400205, https://rscf.ru/project/22-14-00205/ [in Russian]; Assessment of CRISPR/Cas9-based technologies, for A.Yu.R., L.G.M., and S.A.B).

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Authors and Affiliations

  1. Bach Institute of Biochemistry, Federal Research Center of Biotechnology, Russian Academy of Sciences, 119071, Moscow, Russia

    Natalia V. Rassomakhina, Alexandra Yu. Ryazanova, Astemir R. Likhov, Sergey A. Bruskin, Liliya G. Maloshenok & Victoria V. Zherdeva

  2. Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991, Moscow, Russia

    Sergey A. Bruskin & Liliya G. Maloshenok

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  1. Natalia V. Rassomakhina
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  2. Alexandra Yu. Ryazanova
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  3. Astemir R. Likhov
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  4. Sergey A. Bruskin
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  5. Liliya G. Maloshenok
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Contributions

V.V.Zh. developed the concept of the article, wrote and edited the manuscript; N.V.R. developed the concept of the article, wrote and edited the manuscript; A.Yu.R. wrote the text and prepared the tables, edited the manuscript; A.R.L. wrote the text and prepared the tables; S.A.B. and L.G.M. wrote the text and edited the manuscript.

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Correspondence to Victoria V. Zherdeva.

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This work does not contain any studies involving human and animal subjects. The authors of this work declare that they have no conflicts of interest.

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Translated from Uspekhi Biologicheskoi Khimii, 2024, Vol. 64, pp. 247-290.

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Rassomakhina, N.V., Ryazanova, A.Y., Likhov, A.R. et al. Tumor Organoids: The Era of Personalized Medicine. Biochemistry Moscow 89 (Suppl 1), S127–S147 (2024). https://doi.org/10.1134/S0006297924140086

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