Dehydroepiandrosterone (DHEA)-SO₄ Depot and Castration-Resistant Prostate Cancer.

ABSTRACT: Dehydroepiandrosterone (DHEA)-SO₄ of adrenal origin is the major C19 steroid in the serum. It is a precursor of intratumoral androgen biosynthesis in patients with advanced prostate cancer following chemical or surgical castration. DHEA is a product of the P450c17 (17α-hydroxylase-17,20-lyase) enzyme. Despite inhibition of P450c17 with new agents, e.g., Abiraterone acetate, Orterenol, and Galeterone, the level of enzyme inhibition rarely exceeds 90% leaving behind a significant depot for androgen biosynthesis within the tumor. For DHEA-SO₄ to be utilized there is uptake by organic anion transporter polypeptides, deconjugation catalyzed by steroid sulfatase, and adaptive upregulation of prostate steroidogenic enzymes that will convert DHEA into either testosterone or d

SUBMITTER: Penning TM 

PROVIDER: S-EPMC6226251 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature