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Prabhu, A, et al. Cysteine Catabolism: A Novel Metabolic Pathway Contributing to Glioblastoma Growth. Cancer Res, 2014. 74(3):787-96.

Synopsis

Gliomas are type of brain tumor. A better understanding of the underlying biology, particularly of aggressive forms, could aid in identification of new targets for therapy. To aid in advancing this understanding, metabolomics of differentially graded gliomas was performed. The results revealed a striking metabolic node around cysteine metabolism.  This node suggested an upregulation of the enzyme CDO. The upregulation of CDO was validated and shown to be integral to the metabolic reprogramming through inhibition of PDH activity and consequently, oxidative phosphorylation. Importantly, inhibiting CDO activity resulted in growth attenuation of tumors in a mouse model. The results describe a key role of metabolomics in elucidating potential new targets for glioblastoma and should compel investigations into similar metabolic derangements in other tumor types.

Metabolon results led to:

• A potential new target for glioblastomas

• A novel metabolic feature tied to canonical cancer metabolism

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