Androgen deprivation therapy (ADT) is the standard care for advanced prostate cancer (PCa) patients. Unfortunately, although tumors respond well initially, they enter dormancy and eventually progress to fatal/incurable castration-resistant prostate cancer (CRPC).
B7-H3 is a promising new target for PCa immunotherapy. CD276 (B7-H3) gene has a presumptive androgen receptor (AR) binding site, suggesting potential AR regulation. However, the relationship between B7-H3 and AR is controversial. Meanwhile, the expression pattern of B7-H3 following ADT and during CRPC progression is largely unknown, but critically important for identifying patients and determining the optimal timing of B7-H3 targeting immunotherapy. In this study, we performed a longitudinal study using our unique PCa patient-derived xenograft (PDX) models and assessed B7-H3 expression during post-ADT disease progression. We further validated our findings at the clinical level in PCa patient samples. We found that B7-H3 expression was negatively regulated by AR during the early phase of ADT treatment, but positively associated with PCa proliferation during the remainder of disease progression. Our findings suggest its use as a biomarker for diagnosis, prognosis, and ADT treatment response, and the potential of combining ADT and B7-H3 targeting immunotherapy for hormone-naïve PCa treatment to prevent fatal CRPC relapse.
Cancer gene therapy. 2023 Jul 14 [Epub ahead of print]
Ning Kang, Hui Xue, Yen-Yi Lin, Xin Dong, Adam Classen, Rebecca Wu, Yuxuan Jin, Dong Lin, Stanislav Volik, Christopher Ong, Martin Gleave, Colin Collins, Yuzhuo Wang
Department of Experimental Therapeutics, BC Cancer, Vancouver, BC, Canada., Vancouver Prostate Centre, Vancouver, BC, Canada., University of Victoria, Victoria, BC, Canada., Department of Experimental Therapeutics, BC Cancer, Vancouver, BC, Canada. .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/37452083