Polyamine Metabolism as a Metabolic Vulnerability in Prostate Cancer Treated with Supraphysiological Androgens - PubMed
4 hours ago
- #Androgen Therapy
- #Polyamine Metabolism
- #Prostate Cancer
- Prostate cancer progression is primarily driven by androgen receptor (AR) signaling.
- Androgen deprivation therapy (ADT) initially benefits patients but often leads to castration-resistant disease.
- Supraphysiologic androgen (SPA) combined with ADT can suppress tumor growth, though responses vary.
- SPA induces AR-dependent polyamine biosynthesis via ODC1 and AMD1, increasing polyamine synthesis while depleting S-adenosylmethionine (SAM).
- Inhibition of ODC1 with difluoromethylornithine (DFMO) enhances SPA-induced growth suppression by disrupting polyamine pools and worsening SAM depletion.
- A clinical trial combining DFMO with bipolar androgen therapy (BAT) showed reduced polyamines in patients, confirming pathway suppression.
- The study links androgen signaling, polyamine metabolism, and therapeutic response, suggesting metabolic targeting to improve SPA efficacy.