Abstract A21: High-throughput small molecule screening of genetically diverse glioblastoma stem cells

Abstract

Abstract Survival statistics for glioblastoma multiforme (GBM) have remained static despite years of research. Mounting evidence suggests that glioblastoma stem cells (GSCs) are a primary cause of GBM growth, spread, vascularity, and chemotherapeutic resistance. Increasing survival, therefore, demands a therapeutic strategy with efficacy against GSCs. To address this, we have conducted a high-throughput screen of over 3,000 small molecule compounds for activity against three independently derived GSC lines that vary in their expression of TCGA subtype-related genes. Our fluorescence-based assay is sensitive, reliable, and largely free of row- and column-based systematic errors. We identify novel compounds that impair the viability of all three of these genetically diverse GSC lines but have comparably limited toxicity against a normal human glial cell line. Many of these compounds are small and lipophilic, as well, making them ideal candidates for follow-up in vivo evaluation either through intravenous delivery or through encapsulation in polymeric nanoparticles. Citation Format: Garth W. Strohbehn, Jiangbing Zhou, Michael Fu, Toral R. Patel, Joseph M. Piepmeier, W. Mark Saltzman. High-throughput small molecule screening of genetically diverse glioblastoma stem cells [abstract]. In: Proceedings of the AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations; 2012 Jun 27-30; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2012;72(13 Suppl):Abstract nr A21.