Targeting glutamine metabolism network for the treatment of therapy-resistant prostate cancer.
Oncogene
; 41(8): 1140-1154, 2022 02.
Article
en En
| MEDLINE
| ID: mdl-35046532
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Glutamina
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos