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Thesis

Exploring metabolic vulnerability and therapeutic potential in cancers with isocitrate dehydrogenase mutations

Abstract:

Treatment of mutant isocitrate dehydrogenase 1 (IDH1) glioma remains challenging; targeted allosteric inhibitors currently provide limited clinical effect. Resistance to mutIDH1 inhibitors has also emerged in other cancers with mutant IDH1. IDH1 catalyses the decarboxylation of isocitrate to 2-oxoglutarate (2-OG) and concomitant reduction of NADP+ to NADPH. Upon mutation, the enzyme instead reduces 2-OG to (R)-2-hydroxyglutarate (2 HG) with NADPH. 2 HG accumulates to high levels i...

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Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Chemical Biology
Role:
Author

Contributors

Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Role:
Supervisor
ORCID:
0000-0003-4733-1205
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Role:
Examiner
Role:
Examiner
Type of award:
DPhil
Level of award:
Doctoral
Awarding institution:
University of Oxford
DOI:

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