Pharmaceutics & Drug Delivery Systems

Biography

Biography: Hye Jin Jung

Abstract

Glioblastoma stem cells (GSCs) have been proposed as central drivers of tumor progression, treatment resistance and tumor recurrence. Although several molecular markers, such as Wnt, Hedgehog, Notch, TGF-β and EGFR, are known to be useful for targeted therapy in GSCs, exploring novel therapeutic targets and agents to eradicate GSCs can provide a promising treatment strategy that significantly improves glioblastoma patient survival and quality of life. We recently demonstrated that downregulation of mitochondrial ubiquinol−cytochrome c reductase binding protein (UQCRB) and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) inhibits cancer stem cell-like properties in glioblastoma. The treatment with specific inhibitors and siRNAs against the molecular targets significantly inhibited not only the self-renewal capacity, such as cell growth and neurosphere formation, but also the metastasis-promoting ability, such as migration and invasion of GSCs. Notably, the inhibition of stem-like features of glioblastoma cells was associated with the downregulation of mitochondrial ROS/HIF-1a/c-Met and calmodulin/CaMKII/c-Met pathways, resulting in reduction of the expression levels of GSC markers, such as CD133, Nanog, Sox2 and Oct4. These findings suggest that UQCRB and CaMKII could be new therapeutic targets and thus their inhibitors might be utilized as lead compounds for eliminating cancer stem cells in glioblastoma.