Abstract 5474: Biorepository yields potential for personalized medicine approach in pediatric brain cancer patients

Abstract Childhood brain cancer, with a 12% mortality rate, stands as the most lethal cancer among children. Out of the annual 4, 000 diagnoses, 30% involve low-grade gliomas, with a troubling 10% progressing to lethal high-grade gliomas within 2 years. While surgery can often cure the remaining 90%, 50% necessitate adjuvant therapies like chemotherapy and molecular targeting, with radiation sparingly used. Alarmingly, 66% of survivors grapple with long-term health, mental, and cognitive issues due to treatment toxicity, emphasizing the urgent need for innovative biological therapies in pediatric glioma treatment. Our proposed strategy involves the acute analysis of freshly discarded tissue from brain cancer craniotomies, departing from the use of FFPE-preserved tissue, which may exhibit suboptimal quality. All patients provided informed consent, and by prospectively preserving viable tissue, we enable its utilization in ten or more subsequent analyses. These encompass cell-culture-based assays, viability assays, bulk, single cell, and single nucleus RNA sequencing, DNA sequencing, single-cell proteome analyses, flow cytometry, and immunofluorescence. Our findings highlight a direct correlation between surgical sample size and analysis feasibility. Bulk RNA sequencing proves valuable in acutely isolated surgical tissue and cryostored or flash-frozen tissue for identifying novel therapeutic targets in individual patients. Viable cells retrieved from cryopreserved tissue of the same patient allow ex vivo functional validation of therapeutic targets, eliminating the need for establishing patient-derived cell lines and xenografts, particularly challenging for low-grade gliomas. These findings establish the feasibility of a personalized bedside-to-bench approach, contingent on an adequate supply of surgical material. Expanding this approach to encompass all childhood brain cancer types, we plan to investigate using our comprehensive biorepository, housing viable tissue and single-cell suspensions from 122 childhood brain cancer patients. Among these, 51 cases yielded tissue for single-cell RNA-seq and viable cryoprotection. The most common tumor histology identified was low-grade glioma (32), primarily pilocytic astrocytoma (19), followed by embryonal (12) and ependymal tumors (4). In summary, we developed a standard operating procedure for analyzing fresh and cryopreserved surgical discards, identifying novel targets in childhood brain cancer tissue, and functionally validating them in patient-matched samples. This personalized medicine approach holds promise in circumventing the tedious development of patient-derived models. Citation Format: Anna Pronina, Emon Nasajpour, Caitlynn Tran, Troy Schouten, Eden Gibson, Jeffrey Nirschl, Laura Marie Prolo, Kelly Mahaney, Hannes Vogel, Claudia Katharina Petritsch. Biorepository yields potential for personalized medicine approach in pediatric brain cancer patients abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 5474.