2. Academic Validation
  3. Targeting glutamine metabolism network for the treatment of therapy-resistant prostate cancer

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

  • Oncogene. 2022 Feb;41(8):1140-1154. doi: 10.1038/s41388-021-02155-z.
Lingfan Xu 1,  Bing Zhao 1,  William Butler 1,  Huan Xu 1 2,  Nan Song 1 3,  Xufeng Chen 1,  J Spencer Hauck 1,  Xia Gao 4 5,  Hong Zhang 1,  Jeff Groth 1,  Qing Yang 6,  Yue Zhao 1 7,  David Moon 1,  Daniel George 8 9,  Yinglu Zhou 10,  Yiping He 1,  Jiaoti Huang 11 12 13
Affiliations

Affiliations

  • 1 Department of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA.
  • 2 Department of Urology, Shanghai Ninth People's Hospital, Shanghai, China.
  • 3 Department of Urology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
  • 4 Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA.
  • 5 Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.
  • 6 Duke School of Nursing, Duke University, Durham, NC, USA.
  • 7 Department of Pathology, College of Basic Medical Sciences and First Affiliated Hospital, China Medical University, Shenyang, China.
  • 8 Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
  • 9 Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA.
  • 10 Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
  • 11 Department of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA. [email protected].
  • 12 Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA. [email protected].
  • 13 Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA. [email protected].
PMID: 35046532 DOI: 10.1038/s41388-021-02155-z
Abstract

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.

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