The polo-like kinase 1 inhibitor volasertib synergistically increases radiation efficacy in glioma stem cells.

Background: Despite the availability of hundreds of cancer drugs, there is insufficient data on the efficacy of these drugs on the extremely heterogeneous tumor cell populations of glioblastoma (GBM). Results: The PKIS of 357 compounds was initially evaluated in 15 different GSC lines which then led to a more focused screening of the 21 most highly active compounds in 11 unique GSC lines using HTS screening for cell viability. We further validated the HTS result with the second-generation PLK1 inhibitor volasertib as a single agent and in combination with ionizing radiation (IR). Conclusions: Our results reinforce the potential therapeutic efficacy of volasertib in combination with radiation for the treatment of GBM. Methods: We used high-throughput screening (HTS) to identify drugs, out of 357 compounds in the published Protein Kinase Inhibitor Set, with the greatest efficacy against a panel of glioma stem cells (GSCs), which are representative of the classic cancer genome atlas (TCGA) molecular subtypes. Oncotarget 2018; 9(8):10497-10509

EGFR Amplification Induces Increased DNA Damage Response and Renders Selective Sensitivity to Talazoparib (PARP Inhibitor) in Glioblastoma.

PURPOSE: Exploration of novel strategies to extend the benefit of PARP inhibitors beyond EXPERIMENTAL DESIGN: Selective sensitivity to the PARP inhibitor talazoparib was screened and validated in two sets [test set ( RESULTS: CONCLUSIONS