New JCI Study Identifies a Novel Driver of Treatment-Resistant Prostate Cancer

Researchers at the Vancouver Prostate Centre have identified a previously unrecognized mechanism that enables prostate cancer to resist androgen deprivation therapy (ADT), one of the most common treatments for the disease.

In a new study led by Dr. Xuesen Dong and published in the Journal of Clinical Investigation, the team addressed a long-standing paradox in prostate cancer biology: while ADT suppresses tumor growth, levels of the androgen-degrading enzyme UGT2B17 consistently rise in tumors that become resistant to treatment. The study reveals that UGT2B17 has critical roles beyond androgen metabolism. Specifically, it enables prostate cancer cells to withstand ADT-induced stress and continue proliferating through mechanisms that are independent of its enzymatic activity.

Importantly, targeting these newly identified non-enzymatic functions of UGT2B17 significantly slowed tumor growth, highlighting the enzyme as a promising new therapeutic target for patients with advanced, treatment-resistant prostate cancer.

A related study published in European Urology Oncology further underscores the prognostic relevance of UGT2B17, demonstrating its prognostic significance in localized prostate cancer using large, multi-institutional Canadian cohorts. Together, these complementary studies advance understanding of prostate cancer progression and highlight British Columbia’s contributions to national precision oncology efforts.

Primary publication
Feng T, Xie N, Gao L, et al.
Non-canonical functions of UGT2B17 promote castrate-resistant prostate cancer progression.
Journal of Clinical Investigation, 2025.
PMID: 41343245
Link: https://pubmed.ncbi.nlm.nih.gov/41343245/

Related publication
Uchil A, Lacombe L, Hovington H, et al.
European Urology Oncology, 2025.
PMID: 40998686
Link: https://pubmed.ncbi.nlm.nih.gov/40998686/