Related Experiment Video
Updated: Feb 22, 2026
Establishing 3-Dimensional Spheroids from Patient-Derived Tumor Samples and Evaluating their Sensitivity to Drugs
Published on: December 16, 2022
Three-Dimensional Patient-Derived In Vitro Sarcoma Models: Promising Tools for Improving Clinical Tumor Management
Manuela Gaebler1, Alessandra Silvestri2, Johannes Haybaeck3,4
1HELIOS Klinikum Berlin-Buch GmbH, Department of Interdisciplinary Oncology, Berlin, Germany.
Abstract:
Over the past decade, the development of new targeted therapeutics directed against specific molecular pathways involved in tumor cell proliferation and survival has allowed an essential improvement in carcinoma treatment. Unfortunately, the scenario is different for sarcomas, a group of malignant neoplasms originating from mesenchymal cells, for which the main therapeutic approach still consists in the combination of surgery, chemotherapy, and radiation therapy. The lack of innovative approaches in sarcoma treatment stems from the high degree of heterogeneity of this tumor type, with more that 70 different histopathological subtypes, and the limited knowledge of the molecular drivers of tumor development and progression. Currently, molecular therapies are available mainly for the treatment of gastrointestinal stromal tumor, a soft-tissue malignancy characterized by an activating mutation of the tyrosine kinase KIT. Since the first application of this approach, a strong effort has been made to understand sarcoma molecular alterations that can be potential targets for therapy. The low incidence combined with the high level of histopathological heterogeneity makes the development of clinical trials for sarcomas very challenging. For this reason, preclinical studies are needed to better understand tumor biology with the aim to develop new targeted therapeutics. Currently, these studies are mainly based on in vitro testing, since cell lines, and in particular patient-derived models, represent a reliable and easy to handle tool for investigation. In the present review, we summarize the most important models currently available in the field, focusing in particular on the three-dimensional spheroid/organoid model. This innovative approach for studying tumor biology better represents tissue architecture and cell-cell as well as cell-microenvironment crosstalk, which are fundamental steps for tumor cell proliferation and survival.
Insights
Sarcomas lack targeted therapies due to heterogeneity. Three-dimensional spheroid/organoid models offer a promising preclinical approach to understand sarcoma biology and develop new treatments.
Area of Science:
- Oncology
- Molecular Biology
- Translational Medicine
Background:
- Targeted therapeutics have improved carcinoma treatment but not sarcoma care.
- Sarcomas present treatment challenges due to over 70 subtypes and limited knowledge of molecular drivers.
- Current sarcoma treatment relies on surgery, chemotherapy, and radiation, with limited molecular therapies like for gastrointestinal stromal tumors.
Purpose of the Study:
- To review current preclinical models for sarcoma research.
- To highlight the potential of three-dimensional (3D) spheroid/organoid models in understanding sarcoma biology.
- To emphasize the need for innovative models to develop targeted sarcoma therapeutics.
Main Methods:
- Review of existing literature on sarcoma preclinical models.
- Focus on in vitro testing, including cell lines and patient-derived models.
- Detailed examination of three-dimensional spheroid/organoid models.
Main Results:
- Patient-derived models and cell lines are valuable in vitro tools for sarcoma research.
- Three-dimensional spheroid/organoid models offer a more accurate representation of tumor architecture and microenvironment.
- These advanced models facilitate the study of cell-cell and cell-microenvironment interactions crucial for tumor progression.
Conclusions:
- Innovative preclinical models are essential for advancing sarcoma targeted therapy development.
- Three-dimensional spheroid/organoid models show significant promise for overcoming challenges posed by sarcoma heterogeneity.
- Further research using these advanced models can lead to novel therapeutic strategies for sarcoma patients.
