Translating Single Cell Analysis into Actionable Therapeutic Strategies for Glioblastoma

Glioblastoma is a highly lethal malignancy for which effective treatments do not exist. In contrast to many other tumor types, precision medicine approaches based on bulk DNA sequencing have not yielded improvements in survival in GBM. We hypothesize this is due to the following: 1.) Bulk profiling does not detect heterogeneity across individual cells within a tumor (intratumoral heterogeneity) with vastly different phenotypes and drug susceptibilities, and 2.) Assays of DNA mutation do not account for perturbed epigenetic regulation, which can significantly alter the functional consequences of genetic mutations. Novel nongenetic profiling methods at single cell resolution (single cell RNA-seq) overcome these shortcomings to generate epigenetic metadata attributable to individual cancer cells. Single cell transcriptome information can then be used to define ‘cell state’, i.e. the metastable phenotype of a cell at a given moment.

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Sponsor: Kuni Foundation