Title of the Thesis “Shunting of Tryptophan Catabolites in Breast Cancer Metabolism to Prevent Cytotoxicity”

Abstract: A series of metabolic reactions in cells, called the kynurenine pathway, contain several potentially toxic molecules. Efforts to target the kynurenine pathway therapeutically have focused on the first enzyme, Indoleamine-2,3-dioxygenase (IDO1), while the regulation of potentially toxic downstream metabolites has been overlooked. In this thesis, patient survival analysis of The Cancer Genome Atlas (TCGA) public data reveals paradoxically better patient survival in IDO1-high breast cancers, suggesting metabolites in the lower portions of the pathway may reduce tumor burden. In vitro analysis suggests that kynurenine metabolite 3-hydroxyanthranilic acid (3HAA) is toxic to breast cancer cells. High-resolution mass spectrometry (HRMS)-based metabolomics showed breast cancer cells may shunt tryptophan catabolites such as kynurenine into either (noncytotoxic) kynurenic or anthranilic acid to prevent 3HAA accumulation. Together, this suggests a potential new therapeutic strategy where tryptophan catabolite shunting may be prevented to elicit 3HAA-mediated toxicity in cancers. 

September 11, 2025, 9:00 am in AVC 278N

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