EPEN-07. Brain-tumor communication reveals potential new therapeutic targets for pediatric ependymoma

Abstract

Abstract Pediatric brain tumors (PBTs) represent the most common solid malignancies in children and the leading cause of cancer-related deaths. Despite the fact that survival after a high-grade brain tumor diagnosis is slowly improving, overall survival remains poor compared with most other cancers, thereby highlighting the need for new therapies. This is particularly true for Ependymoma (EPN), the second most common PBT that, despite advances in the understanding of EPN biology, still shows a poor prognosis in approximately 40% of patients. Accumulative evidence reveals that the transcriptome of tumors can be modulated by the host tissue, with brain tumors or brain metastasis derived from extracranial tumors being at the forefront of these studies. Our hypothesis is that understanding the impact of brain-tumor communication may open up new opportunities for therapeutic intervention. To characterize gene expression changes in Ependymoma tumors caused by the tumor microenvironment the transcriptome of patient-derived EPN cells was analyzed comparing in vitro cultured cells, subcutaneous xenografts and orthotopic xenografts. 2734 differentially expressed genes were found after comparing in vitro grown cells versus brain xenografts. Sixty-five of those genes were also differentially expressed when comparing human expression data from aggressive EPN versus the rest of EPN tumours. Among these candidates NTRK2 and CALB2 stand out. Gene depletion phenotype using multiple shRNA showed that the in vivo tumor growth of NTRK2-depleted cells, (but not CALB2) was remarkably reduced compared with control cells. These results suggest that NTRK2 could be a potential new therapeutic target for the treatment of Ependymoma