TAK-242 inhibits glioblastoma invasion, migration, and proneural-mesenchymal transition by inhibiting TLR4 signaling.

Resatorvid (TAK-242), a small-molecule inhibitor of Toll-like receptor 4 (TLR4), has the ability to cross the blood-brain barrier (BBB). In this study, we explored the role of TAK-242 on glioblastoma (GBM) invasion, migration, and proneural-mesenchymal transition (PMT). RNA sequencing (RNA-Seq) data and full clinical information of glioma patients were downloaded from the Chinese Glioma Genome Atlas (CGGA) and the Cancer Genome Atlas (TCGA) cohorts and then analyzed using R language; patients were grouped based on proneural (PN) and mesenchymal (MES) subtypes.

PLK1 inhibition promotes apoptosis and DNA damage in glioma stem cells by regulating the nuclear translocation of YBX1.

Glioma stem cells (GSCs) are the important cause of tumorigenesis, recurrence, and chemo(radio)resistance in glioma. Targeting GSCs helps improve the outcomes of glioma treatment. Polo-like kinase 1 (PLK1) is a member of the serine/threonine protein kinase family, which is highly conserved.

BRD4 regulates self-renewal ability and tumorigenicity of glioma-initiating cells by enrichment in the Notch1 promoter region.

Bromodomain and extraterminal domain (BET) family proteins are considered to be epigenetic readers that regulate gene expression by recognizing acetyl lysine residues on histones and nonhistone chromatin factors and have been classified as curative targets for a variety of cancers. Glioma-initiating cells (GICs), which commit self-renewal, perpetual proliferation, multidirectional differentiation, and vigorous tumorigenicity, sustain the peculiar genetic and epigenetic diversification in the GBM patients, thus, GICs result in tumor recurrence. Abundant evidence demonstrates that BET proteins regulate differentiation of stem cells.

Dual PLK1 and STAT3 inhibition promotes glioblastoma cells apoptosis through MYC.

Glioblastoma (GBM) is the deadliest primary brain tumor that is highly resistant to current treatments. Polo-like kinase 1 (PLK1) and signal transducer and activator of transcription 3 (STAT3) are highly expressed in gliomas, especially GBM. Previous studies have shown reciprocal activation between PLK1 and STAT3 and that they regulate the same pools of MYC downstream.