Research ArticleGlioblastoma

Targeting pyrimidine synthesis accentuates molecular therapy response in glioblastoma stem cells

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Science Translational Medicine  07 Aug 2019:
Vol. 11, Issue 504, eaau4972
DOI: 10.1126/scitranslmed.aau4972

Targeting metabolic changes in glioblastoma

Glioblastoma (GBM) is the most aggressive brain cancer in adults. GBM stem cells (GSCs) contribute to tumor initiation and therapeutic resistance. Understanding the metabolic alterations in GSCs could help the development of new therapeutic strategies. Now, Wang et al. revealed that pyrimidine biosynthesis is up-regulated in GSCs and correlated with tumor grade in patients with GBM. This metabolic alteration was necessary for GSC maintenance, and combined targeting of pyrimidine synthesis and tumor-specific driver mutations using approved drugs improved survival and inhibited tumor growth compared to the single treatments in mouse models. Targeting metabolic reprogramming in combination with mutation-specific therapies might improve clinical outcome in patients with GBM.

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