Biol-20. bioprocessing of surgical pediatric brain tumor specimens for genome-guided personalized drug testing

Abstract Novel treatment approaches are urgently needed for pediatric central nervous system (CNS) tumors as they are the leading cause of cancer-related deaths in children. A lack of research materials impedes progress towards developing such therapies. Although various brain cancer biobanks exist, these rarely store viable patient-derived tissue and cells for live cell analyses, including cell fate assays and testing for drug sensitivities. We propose that a biorepository of viable cell dissociates and tissue broadly representing CNS tumor entities overcomes these limitations. From a combination of molecular diagnoses and histopathologic assessment of over 90 samples collected, we generated a biorepository of roughly 35 distinct entities of pediatric CNS tumors in our Stanford neuro-bioprocessing cohort. Based on the Central Brain Tumor Registry of the United States, the proportion of subtypes represented in our cohort match that of the general population with exceptions. We established a standardized bioprocessing pipeline that can be used as a template for tissue collection and model development in the broader disease context and for multiple downstream applications. Our emphasis on cryostorage of viable cells and tissue facilitates ad hoc live cell analyses. In addition to gaining a better understanding of tumor pathophysiology, we attempted a rapid bed-to-bench-to-bedside approach using comparative RNA expression profile analyses in an individual patient’s pilocytic astrocytoma. Novel drug targets were identified by analyzing RNA transcripts that are highly expressed (outliers) compared with a compendium of 12,747 brain and non-brain tumor samples. We validated outliers as drug targets using acute cell isolates, and identified a novel target in recurrent low-grade glioma. These studies illustrate that biobanking of viable patient-derived material enables developing personalized therapies with the goal of improving patient outcomes. As demonstrated here, patient-derived acute cell isolates facilitate identifying drug vulnerability, creating an opportunity for more personalized treatment of patients with CNS tumors.