Metabolic molecule drives growth of aggressive brain cancer
A study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) has identified an abnormal metabolic pathway that drives cancer-cell growth in a particular glioblastoma subtype. The finding might lead to new therapies for a subset of patients with glioblastoma, the most common and lethal form of brain cancer. The physician scientists sought to identify glioblastoma subtype-specific cancer stem cells. Genetic analyses have shown that high-grade gliomas can be divided into four subtypes: proneural, neural, classic and mesenchymal.
- Genes involved in glycolysis and gluconeogenesis, particularly ALDH1A3, were significantly up-regulated in mesenchymal glioma stem cells compared to proneural stem cells;
- Mesenchymal glioma stem cells show significantly higher radiation resistance and high expression of DNA-repair genes;
- Radiation induces transformation of proneural glioma stem cells into mesenchymal-like glioma stem cells that are highly resistant to radiation treatment; inhibiting the ALDH1 pathway reverses this resistance.
- Inhibiting ALDH1A3-mediated pathways slows the growth of mesenchymal glioma stem cells and might provide a promising therapeutic approach for glioblastomas with a mesenchymal signature.
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