Targeting glutamine metabolism network for the treatment of therapy-resistant prostate cancer.

Journal Article (Journal Article)

Advanced and aggressive prostate cancer (PCa) depends on glutamine for survival and proliferation. We have previously shown that inhibition of glutaminase 1, which catalyzes the rate-limiting step of glutamine catabolism, achieves significant therapeutic effect; however, therapy resistance is inevitable. Here we report that while the glutamine carbon is critical to PCa survival, a parallel pathway of glutamine nitrogen catabolism that actively contributes to pyrimidine assembly is equally important for PCa cells. Importantly, we demonstrate a reciprocal feedback mechanism between glutamine carbon and nitrogen pathways which leads to therapy resistance when one of the two pathways is inhibited. Combination treatment to inhibit both pathways simultaneously yields better clinical outcome for advanced PCa patients.

Full Text

Duke Authors

Cited Authors

  • Xu, L; Zhao, B; Butler, W; Xu, H; Song, N; Chen, X; Spencer Hauck, J; Gao, X; Zhang, H; Groth, J; Yang, Q; Zhao, Y; Moon, D; George, D; Zhou, Y; He, Y; Huang, J

Published Date

  • February 2022

Published In

Volume / Issue

  • 41 / 8

Start / End Page

  • 1140 - 1154

PubMed ID

  • 35046532

Electronic International Standard Serial Number (EISSN)

  • 1476-5594

Digital Object Identifier (DOI)

  • 10.1038/s41388-021-02155-z

Language

  • eng

Conference Location

  • England