Metabolic reprogramming is one of the key hallmarks in acquiring aggressive phenotype and chemoresistance in many cancers including T-cell acute lymphoblastic leukemia (T-ALL). To combat chemoresistance, we treated patient-derived xenografts with two metabolic drugs that target two different pathways for T-ALL: IACS-010759, a Complex I inhibitor for OXPHOS pathway and AZD3965, a monocarboxylate transporter-1 (MCT1) inhibitor. Hyperpolarized metabolic imaging in vivo and NMR metabolomics ex vivo was utilized to observe the difference in metabolism with single treatment and in combination. Our results demonstrate that metabolic intervention utilizing OXPHOS blockade can be potentiated by targeting the MCT1 transporter.
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