PNAs: discovery of drugs that can kill glioma stem cells efficiently

March 15, 2019 / bioun / Scripps Institute (TSRI) scientists have found a compound that can selectively and efficiently kill brain glioma stem cells, which makes brain glioma so deadly Photo source: the PNAs study was published in PNAS recently Scientists from TSRI found that a compound they named ripgbm can kill glioma stem cells from patients' tumors The killing effect is 40 times that of temozolomide, the standard treatment drug for glioma They also found that ripgbm is highly selective and does not kill other kinds of brain cells, while significantly inhibiting the growth of gliomas in mice "Our findings provide a promising new approach for the treatment of gliomas." Dr Luke lairson, an associate professor of chemistry at TSRI and a corresponding author of the study, said Every year, 10000 people in the United States are diagnosed with glioma, which is difficult to treat The median survival time after diagnosis is only one year Past studies have found that glioblastoma cancer stem cells (GBM CSCs) are the key to such a deadly tumor GBM CSCs have strong tolerance to chemotherapy and radiotherapy, and will migrate from primary tumor to surrounding healthy brain tissue Even after surgical resection of tumor tissue and standard chemotherapy and radiotherapy, there will still be some GBM CSCs left in the brain of patients, which will eventually generate new tumors Lairson and his colleagues designed an automatic high-throughput screening method to screen a large number of small molecular compounds, using them to process healthy brain cells and GBM CSCs from GBM patients' tumors "These cells from the patient maintain the lethal characteristics of tumor cells, including the ability to inject into the mouse brain to form GBM like tumors." Lairson said After several rounds of screening, lairson and his colleagues found the compound ripgbm, which can kill GBM CSCs efficiently without damaging normal brain cells They found that it was selective because it was modified by specific enzymes or factors in GBM CSCs In these tumor cells, the modified kripgbm can induce apoptosis Scientists found that after transplanting the glioma cells from patients, the mice will form large brain tumors within 5 weeks, while the mice treated with ripgbm can only form small brain tumors Lairson and colleagues plan to further develop ripgbm, and if it goes well, more animal experiments and human clinical experiments will be carried out "In principle, small molecules such as ripgbm can significantly reduce the growth of glioma without serious side effects, because it does not damage normal brain cells." Reference: Natasha C lucky et al A cell type selective apoptosis inducing small motion for the treatment of brain cancer, procedures of the National Academy of Sciences (2019) Doi: 10.1073/pnas.1816626116