Establishing a pediatric solid tumor PDX biobank for precision oncology research

Author(s):Show less -

Akemi Kido, Larissa ; Rodrigues Marusco, Milena ; Aparecida da Silva, Ellen ; Do Carmo, Lais ; Beatriz Teodoro Borges, Ana ; Luz Torres Silva, Felipe ; Silveira Ruas, Juliana ; Giomo de Lima, Dieila ; de Abreu Fernandes, Larissa ; Maia Martin Daiggi, Camila ; Aparecida Cardinalli, Izilda ; Ferreira Euzebio, Mayara ; Yoshioka Jotta, Patricia ; Maschietto, Mariana ; Pini Zenatti, Priscila

• Document type: Journal article
• Source: CANCER BIOLOGY & THERAPY; v. 26, n. 1, p. 16-pg., 2025-12-31.

Abstract

Developing advanced preclinical models and targeted therapies is essential for reducing cancer-related deaths in children with solid tumors. Patient-derived xenografts (PDX) have the potential to replicate key elements of the original tumor, including morphology, genetic alterations, and microenvironment, making them valuable tools for studying tumor biology and drug response. We implanted 124 pediatric solid tumor samples, collected for 1 y, into NOD/SCID/IL2Rg (NSG) mice. Tumor fragments were placed subcutaneously, and the animals were monitored for up to 1 y. Histopathology, Short Tandem Repeat (STR) profiling, RT-PCR and/or RNA-sequencing were performed to confirm tumor identity and detect driver fusions. Fifty-five xenografts were successfully established (44.35% of implanted samples), representing 19 tumor types. Sarcomas, notably osteosarcoma, Ewing sarcoma, synovial sarcoma, and rhabdomyosarcoma, displayed first-generation engraftment rates above 55%. Central nervous system tumors had lower success, reflecting unique microenvironmental requirements. Histopathology and STR concordances were 85.45% and 81.1%, respectively, while 92.6% of sarcoma PDXs retained original fusion genes. Second-generation xenografts showed faster growth, suggesting adaptation to the murine host. Sporadic discrepancies, such as new fusions or lymphoproliferative expansions, indicated the need for ongoing molecular validation parallel to other techniques. A pediatric PDX biobank can effectively capture key tumor features while facilitating the study of therapeutic responses and tumor evolution. Our models confirm the feasibility of achieving stable histological and molecular profiles, offering a valuable resource for precision oncology research. Ultimately, these pediatric PDXs could accelerate the discovery of targeted therapy and significantly improve treatment outcomes. (AU)

• FAPESP's process: 23/14392-0 - Histopathological profiling of pediatric synovial sarcoma PDX (Patient-Derived Xenograft) samples and the establishment of spheroid (3D) cell culture."
• Grantee: Larissa de Abreu Fernandes
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 22/04781-6 - Search for the molecular mechanisms involved with the tumorigenesis of bone tumors
• Grantee: Felipe Luz Torres Silva
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 21/04137-7 - Monoclonal antibodies against pediatric Acute Lymphoblastic Leukemia
• Grantee: Priscila Pini Zenatti Salles
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 21/06782-7 - Striking the evolutionary process of bone tumors
• Grantee: Mariana Camargo Maschietto
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2