EXTH-28. INTRATUMORAL HETEROGENEITY OF THERAPEUTIC VULNERABILITIES ACROSS ENHANCING AND NON-ENHANCING TUMOR COMPONENTS OF GLIOBLASTOMA: A PARADIGM-SHIFTING PERSONALIZED MEDICINE APPROACH

Abstract Glioblastoma (GBM) is the most aggressive adult brain tumor with no effective therapy. Despite advances on its molecular characterization, targeted therapeutics remain out of reach. This lack-of-progress largely attributed to and spatial heterogeneity absence clinically applicable models guide patient care. Moreover, as standard surgical resection aimed at contrast-enhancing (CE) tumor, landscape treatment response remaining non-contrast enhancing (nCE) component unknown despite active role in progression local recurrence. Here, we identify functional impact explore therapeutic vulnerabilities both CE nCE components. Four regions (two two nCE) from each five GBM patients were collected under neuronavigation. The resulting tissue was subjected generation 3D (a initiating-enriched cell line a spheroid-based mcancer model) comparable success samples. A panel 25 penetrant drugs (alone combination) targeting drivers (i.e. RTK/Ras/PI3K, RB/cell cycle, p53/apoptosis, DNA damage repair, transcription addiction) developed used test for vulnerabilities. From region, 4.5 ± 3.7 (average SD) different strategies identified exhibiting least 70% growth inhibition Cmax. Drug relatively rare, varied among cases, independent enhancement status. To our knowledge, this first study systemically assess patient-derived models. Ongoing studies include comprehensive genome transcriptome profiling pathway analysis these regions. We postulate that interrogation landscapes vulnerability profiles regions, will enable us personalize prioritize interventions treatment.