Research ArticleCancer

Metabolic reprogramming toward oxidative phosphorylation identifies a therapeutic target for mantle cell lymphoma

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Science Translational Medicine  08 May 2019:
Vol. 11, Issue 491, eaau1167
DOI: 10.1126/scitranslmed.aau1167

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Dismantling lymphoma metabolism

Mantle cell lymphoma is a B cell malignancy that often responds to initial treatment with ibrutinib, an inhibitor of Bruton’s tyrosine kinase. Unfortunately, the therapeutic response is typically short lived for reasons that are not yet fully understood. Zhang et al. found that resistance to ibrutinib in mantle cell lymphoma can be associated with metabolic reprogramming and a shift toward reliance on glutaminolysis and oxidative phosphorylation by the cancer cells. The authors demonstrated that these drug-resistant cells can be effectively targeted with a small-molecule inhibitor of oxidative phosphorylation, showing promising therapeutic results in patient-derived mouse models.