Remodeling of androgen metabolism network mediated by UGT2B: a new perspective on treatment resistance in prostate cancer.

Prostate cancer (PCa) is the most common and aggressive malignancy in males worldwide, with its progression influenced by multiple factors. Androgens, the primary regulators of prostate cell growth and physiology, play a pivotal role in PCa pathogenesis through the androgen receptor (AR) signaling pathway, thus earning PCa designations as a hormone-sensitive or hormone-dependent cancer. Current anti-androgen therapies (e.g., androgen deprivation therapy, ADT) have demonstrated initial effectiveness but ultimately failed to prevent progression to castration-resistant prostate cancer (CRPC). Previous research has predominantly focused on AR and its associated signaling pathways. However, UGT2B15 and UGT2B17, as key members of the human UDP-glucuronosyltransferase (UGT) family, serve as critical catalytic enzymes in androgen metabolism. They both efficiently convert androgens into more excretable glucuronidated metabolites, thereby modulating systemic hormone levels, primarily affecting the activation of AR. This article systematically explores the association between the UGT2B subfamily and hormone-dependent prostate cancer, covering various aspects such as gene function, regulatory mechanisms, disease progression, and diagnosis. It elucidates the different roles of UGT2B genes and reveals their significant potential in being developed into biomarkers and therapeutic targets, paving the way for improvements in precision medicine for prostate cancer.