Establishing a pediatric solid tumor PDX biobank for precision oncology research

Area of Science:

• Oncology
• Translational Research
• Preclinical Models

Background:

• Pediatric solid tumors require advanced preclinical models for effective targeted therapy development.
• Patient-derived xenografts (PDX) offer a promising approach to recapitulate tumor heterogeneity and microenvironment.

Purpose of the Study:

• To establish and characterize a biobank of pediatric solid tumor patient-derived xenografts (PDX).
• To assess the fidelity of PDX models in preserving tumor morphology, genetic alterations, and fusion genes.
• To evaluate the potential of PDX models for studying tumor biology and therapeutic responses in pediatric cancers.

Main Methods:

• Implantation of 124 pediatric solid tumor samples into NOD/SCID/IL2Rg (NSG) mice.
• Monitoring of tumor growth and characterization using histopathology, Short Tandem Repeat (STR) profiling, RT-PCR, and RNA-sequencing.
• Assessment of first- and second-generation xenograft engraftment rates and molecular stability.

Main Results:

• Successfully established 55 pediatric PDX models (44.35% engraftment rate) across 19 tumor types.
• High engraftment rates (>55%) observed for sarcomas, including osteosarcoma and Ewing sarcoma.
• High concordance (85.45% histopathology, 81.1% STR) and retention of driver fusion genes (92.6% in sarcoma PDXs) confirmed model fidelity.
• Second-generation xenografts demonstrated accelerated growth, indicating host adaptation.

Conclusions:

• Pediatric PDX models effectively capture key histological and molecular features of original tumors.
• These models serve as a valuable resource for precision oncology, facilitating targeted therapy discovery and the study of tumor evolution.
• The established PDX biobank demonstrates feasibility and potential to accelerate development of novel treatments for pediatric solid tumors.