Abstract

A fresh look at glutamine targeting Glutamine is essential for tumor growth and has long been an attractive therapeutic target for cancer researchers. Some attempts at blocking glutamine metabolism in cancer patients resulted in toxicity, prompting Leone et al. to develop an innovative approach to reduce general side effects. They designed a prodrug form (JHU083) of the glutamine antagonist 6-diazo-5-oxo- l -norleucine (DON), which is administered in an inert state but then preferentially activated by enzymes enriched in the tumor microenvironment. JHU083 simultaneously shut down glycolysis and oxidative phosphorylation in mouse cancer cells while enhancing T cell oxidative phosphorylation and anticancer immune responses. Science , this issue p. 1013

Keywords

GlutamineEffectorImmune systemImmunotherapyBiologyTumor microenvironmentBlockadeCancer cellGlutaminolysisCancer researchMetabolismCell biologyCancerImmunologyBiochemistryReceptorAmino acid

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Publication Info

Year
2019
Type
article
Volume
366
Issue
6468
Pages
1013-1021
Citations
1056
Access
Closed

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Robert D. Leone, Liang Zhao, Judson M. Englert et al. (2019). Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion. Science , 366 (6468) , 1013-1021. https://doi.org/10.1126/science.aav2588

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DOI
10.1126/science.aav2588