Assessment of the effectiveness of the use of tumoroids for personalized drug therapies for solid tumors

The approach to the management of cancerous neoplasms, which aims to define the effective curative strategies in each patient, defines the requirement for the elaboration and use of modelling systems that replicate the structures and the biology of human solitary tumors. Three-dimensional cultures of spheroids/tumoroids, which are multi-cell aggregates of malignized cells, can create the intercellular connections of interest, gradients of the nutrients and oxygen, and cell polarity, all of which are absent in the conventional two-dimensional single-layer system. The present work is dedicated to a comparison study of in vitro viability and invasiveness of solid tumor cells of patients under the effect of chemopreparations and their combinations in view of evaluating the efficacy of the 3D-cell modelling system in the translational personalized medicine context. Cell cultures of patients who were treated at the N.N. Petrov National Medicine Research Center of oncology were used as a basis for the development of 3D-cell models. N.N. Petrov NMRC in 2015-2021. Tumor tissue pieces were acquired intraoperatively: 1 - leiomyosarcoma (LMS), 1 - rhabdomyosarcoma (RMS), 1 - synovial sarcoma (SS), 2 - myxofibrosarcoma (MFS), 2 - osteogenic sarcoma (OS), 1 - skin melanoma (MC), 1 - breast cancer (BC) (n=9). Our individual comparison of the effectiveness of in vitro chemotherapeutic agents against tumor cells of various origins cultivated in 2D and 3D model systems with real clinically relevant cases confirmed that the monolayer culture as the test system was less adequate for selecting and personalizing the treatment of malignant tumor patients: the 3D cell system proved itself in 77.7% of cases, and the monolayer culture - in 44.4% of cases. The combination of doxorubicin/iforsfamide and paclitaxel significantly suppressed the motility in the matrigel of spheroid cells, but did not affect tumor cell viability, which was seen in all but OS #921 and MK #929 cases. The cultivation of tumor cells in form of spheroids/tumoroids allows to utilize them as more adequate pre-clinical model as individual predictive test-system, enabling the personalized selection of therapy.