Concise Review: Bullseye: Targeting Cancer Stem Cells to Improve the Treatment of Gliomas by Repurposing Disulfiram

摘要: Cancer stem cells (CSCs) are thought to be at the root of cancer recurrence because they resist conventional therapies and subsequently reinitiate tumor cell growth. Thus, targeting CSCs could bullseye successful therapeutics in future. Brain tumors some most challenging types treat median survival following initial diagnosis is 12-18 months. Among different brain tumors, glioblastoma (GBM) considered aggressive remains extremely difficult treat. Despite surgery, radiation, chemotherapy, patients develop refractory disease. Temozolomide (TMZ) a chemotherapy used GBM however resistance develops patients. The underlying mechanisms for TMZ (TMZ-resistant) involve expression DNA repair gene O(6)-methylguanine-DNA methyltransferase. CSC genes such as Sox-2, BMI-1, more recently Y-box binding protein-1 also play role resistance. In order novel GBM, libraries small interfering RNAs off-patent drugs have been screened. Over past few years, several independent laboratories identified disulfiram (DSF) an drug that kills CSCs. Reportedly DSF has modes action including its ability inhibit aldehyde dehydrogenases, E3 ligase, polo-like kinase 1, NFkB. Due fact disease heterogeneity, with multitargeting properties may way broader terms, from range further supporting idea repurposing it "target practice."