Inhibition of Glutamine Metabolism Attenuates Tumor Progression Through Remodeling of the Macrophage Immune Microenvironment.

ABSTRACT: Targeting glutamine metabolism has emerged as a promising strategy in cancer therapy. To attain clinical utility, a number of challenges must be overcome, including in vivo anti-tumor activity, pharmacological toxicity, and clinical safety. Aside from glutamine-addicted tumor cells, immune cells may also need glutamine to sustain physiological activities; thus, the current work used two immunological-intact murine cancer models to assess the effects of glutamine antagonists on tumor cells and the immune milieu. To minimize potential off-target effects, we developed a glutamine antagonist prodrug, JHU083, which is bioactivated selectively in cancer tissues. In both murine tumor models, we observed a significant anti-tumor effect, resulting in reduced tumor burden and impeded tumor progressi

SUBMITTER: Li T 

PROVIDER: S-EPMC12517317 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature