New lab-grown organoids accurately mimic pediatric brain tumor biology

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

These models utilize the latest technical advances, allowing researchers to perform functional assays and preclinical drug testing faster without relying on newly obtained tumor samples. The models are available to other researchers upon request, providing a resource to help advance the field. The work was published today in Science Advances.

Pediatric brain and central nervous system tumors are among the leading causes of disease-related death in children in the United States each year. Traditional models, such as patient-derived orthotopic xenografts, retain tumor features 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, St. Jude Department of Tumor Cell Biology.

By developing lab-grown tumor organoids that truly reflect the original tumors they came from, we created a faster, more accessible way for researchers to study these tumors and test potential therapies."

Martine Roussel, St. Jude Children's Research Hospital

Modeling brain tumors with 3D organoids

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

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

Importantly, the researchers have made the organoid models available to the wider scientific community. "Not everyone has the resources to develop these types of models," explained Roussel."These organoids are available to researchers upon request, allowing more scientists to use them to advance the study of pediatric brain tumors."