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Updated: Sep 2, 2025
Tumorsphere Derivation and Treatment from Primary Tumor Cells Isolated from Mouse Rhabdomyosarcomas
Published on: September 13, 2019
Mesenchymal tumor organoid models recapitulate rhabdomyosarcoma subtypes
Michael T Meister1,2, Marian J A Groot Koerkamp1,2, Terezinha de Souza1,2
1Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Abstract:
Rhabdomyosarcomas (RMS) are mesenchyme-derived tumors and the most common childhood soft tissue sarcomas. Treatment is intense, with a nevertheless poor prognosis for high-risk patients. Discovery of new therapies would benefit from additional preclinical models. Here, we describe the generation of a collection of 19 pediatric RMS tumor organoid (tumoroid) models (success rate of 41%) comprising all major subtypes. For aggressive tumors, tumoroid models can often be established within 4-8 weeks, indicating the feasibility of personalized drug screening. Molecular, genetic, and histological characterization show that the models closely resemble the original tumors, with genetic stability over extended culture periods of up to 6 months. Importantly, drug screening reflects established sensitivities and the models can be modified by CRISPR/Cas9 with TP53 knockout in an embryonal RMS model resulting in replicative stress drug sensitivity. Tumors of mesenchymal origin can therefore be used to generate organoid models, relevant for a variety of preclinical and clinical research questions.
Insights
New pediatric rhabdomyosarcoma (RMS) organoid models were created to improve preclinical research. These tumoroid models closely resemble original tumors and enable personalized drug screening for better childhood cancer therapies.
Area of Science:
- Oncology
- Developmental Biology
- Biotechnology
Background:
- Rhabdomyosarcomas (RMS) are the most common childhood soft tissue sarcomas, originating from mesenchymal cells.
- Current treatments for high-risk RMS patients have a poor prognosis, necessitating novel therapeutic strategies.
- The development of advanced preclinical models is crucial for discovering new treatments for pediatric RMS.
Purpose of the Study:
- To generate and characterize a collection of pediatric rhabdomyosarcoma tumoroid models.
- To assess the feasibility of using these models for personalized drug screening.
- To evaluate the genetic stability and utility of tumoroid models in preclinical research.
Main Methods:
- Generation of 19 pediatric rhabdomyosarcoma tumoroid models from various subtypes.
- Comprehensive molecular, genetic, and histological characterization of the generated models.
- Assessment of genetic stability over 6 months of culture and drug screening, including CRISPR/Cas9 modification.
Main Results:
- A 41% success rate in generating tumoroid models, with rapid establishment for aggressive tumors (4-8 weeks).
- Models demonstrated high fidelity to original tumors in molecular, genetic, and histological features.
- Tumoroids showed genetic stability and accurately reflected drug sensitivities, with successful TP53 knockout demonstrating altered drug response.
Conclusions:
- Pediatric rhabdomyosarcoma tumoroid models are feasible and valuable preclinical tools.
- These models closely mimic patient tumors, supporting personalized drug screening and therapeutic development.
- Organoid models derived from mesenchymal tumors offer broad applicability for preclinical and clinical research questions.
