REVIEW: Tumor Organoids: The Era of Personalized Medicine

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Natalia V. Rassomakhina¹, Alexandra Yu. Ryazanova¹, Astemir R. Likhov¹, Sergey A. Bruskin^1,2, Liliya G. Maloshenok^1,2, and Victoria V. Zherdeva^1,a*

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

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

Received October 3, 2023; Revised November 1, 2023; Accepted November 9, 2023

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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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KEY WORDS: 3D tumor organoids, precision medicine, patient-derived tumor organoids (PDTOs), induced pluripotent stem cells (iPSCs), chemotherapy, targeted therapy, immunotherapy, immune checkpoints, personalized therapy, programmed cell death

DOI: 10.1134/S0006297924140086

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