Transcriptomics-Based Phenotypic Screening Supports Drug Discovery in Human Glioblastoma Cells.

ABSTRACT: We have used three established human glioblastoma (GBM) cell lines-U87MG, A172, and T98G-as cellular systems to examine the plasticity of the drug-induced GBM cell phenotype, focusing on two clinical drugs, the phosphodiesterase PDE10A inhibitor Mardepodect and the multi-kinase inhibitor Regorafenib, using genome-wide drug-induced gene expression (DIGEX) to examine the drug response. Both drugs upregulate genes encoding specific growth factors, transcription factors, cellular signaling molecules, and cell surface proteins, while downregulating a broad range of targetable cell cycle and apoptosis-associated genes. A few upregulated genes encode therapeutic targets already addressed by FDA approved drugs, but the majority encode targets for which there are no approved drugs. Amongst the latt

SUBMITTER: Shapovalov V 

PROVIDER: S-EPMC8345128 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature