New organoids grown in lab accurately mimic pediatric brain tumor biology

Efforts to identify and evaluate next-generation therapeutics for pediatric brain tumors are easily hampered by the quality and availability of laboratory models for research. To address this issue, scientists at St. Jude Children’s Research Hospital have developed patient-derived tumor organoids and tumor organoid xenografts that accurately reflect the biological underpinnings of embryonic brain tumors.

These models utilize the latest technological advances, allowing researchers to rapidly perform functional testing and preclinical drug testing without relying on newly obtained tumor samples. The models are available to other researchers upon request, providing a resource to help advance the field. This work was published today science advancement.

Tumors of the pediatric brain and central nervous system are the leading causes of disease-related death in children each year in the United States. Traditional models, such as patient-derived orthotopic xenografts, retain tumor characteristics but are expensive and time-intensive to establish.

“Some patient-derived tumor models can take months to develop, which slows research and increases costs,” said corresponding author Martine Roussel, PhD, of the St. Jude Department of Tumor Cell Biology.

“By developing lab-grown tumor organoids that exactly mirror the original tumor, we have created a faster, more accessible way for researchers to study these tumors and test potential treatments.”

Martine Roussel, St. Jude Children’s Research Hospital

Modeling brain tumors with 3D organoids

Organoids (patient-derived 3D tumor models created in the laboratory) and tumor organoid xenografts (organoids transplanted into immunodeficient mice) are among the most advanced ways to model human cancer in a laboratory setting. For this work, Roussel’s team developed models based on several types of pediatric brain tumors, including medulloblastoma, embryonal tumors with multilayer rosettes, and atypical teratoid rhabdoid tumors.

Molecular analyses, including DNA methylation, bulk and single-cell RNA sequencing, and whole-genome sequencing, revealed that the models faithfully retain the genetic, epigenetic, and cellular diversity of the original tumors. Drug testing showed that the organoids responded similarly to their corresponding tumor organoid xenografts, supporting the efficacy of the models and their value for preclinical studies.

The important thing is that researchers have made organoid Models available to the wider scientific community. “Not everyone has the resources to develop these types of models,” Roussel explained.“These organoids are available To researchers upon request, Allowing more scientists to use them to advance the study of pediatric brain tumors.”