Androgen receptor drives polyamine synthesis creating a vulnerability for prostate cancer.

ABSTRACT: Supraphysiological androgen (SPA) treatment can paradoxically restrict growth of castration-resistant prostate cancer with high androgen receptor (AR) activity, which is the basis for use of Bipolar Androgen Therapy (BAT) for patients with this disease. While androgens are widely appreciated to enhance anabolic metabolism, how SPA-mediated metabolic changes alter prostate cancer progression and therapy response is unknown. Here, we report that SPA markedly increased intracellular and secreted polyamines in prostate cancer models. AR binding at enhancer sites upstream of the ODC1 promoter increased the abundance of ornithine decarboxylase (ODC), a rate-limiting enzyme of polyamine synthesis, and de novo synthesis of polyamines from arginine. SPA-stimulated polyamines enhanced prostate cance

SUBMITTER: Kumar R 

PROVIDER: S-EPMC12758111 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature