Abstract
Abstract Glioblastoma (GBM) remains the most common and lethal adult primary brain cancer. Two of the most significant issues preventing the development of effective GBM treatments are inter- and intra-tumor heterogeneity. To address these issues, we developed a novel platform termed ISOSCELES (Inferred cell Sensitivity Operating on the integration of Single-Cell Expression and L1000 Expression Signatures). ISOSCELES integrates single-cell gene expression data in individual GBM tumors with perturbation-response data derived from the NIH Library of Integrated Network-Based Cellular Signatures (LINCS) L1000 dataset to predict sensitive and resistant tumor cell populations. Importantly, we analyzed the predictive power of ISOSCELES in an in vivo xenograft model and demonstrated that ISOSCELES reveals the GBM cell identities primed for lineage expansion during treatment with the aurora kinase inhibitor alisertib. These studies suggest that ISOSCELES can be used to identify sensitive and resistant cell populations to targeted therapies in GBM, which can inform treatment decisions in ongoing and future clinical trials.
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