前列腺癌
雄激素剥夺疗法
医学
免疫疗法
生物标志物
肿瘤科
癌症
雄激素受体
内科学
癌症研究
生物
生物化学
作者
Ning Kang,Hui Xue,Yen-Yi Lin,Xin Dong,Annika Y. Claßen,Rebecca Wu,Yuxuan Jin,Dong Lin,Stanislav V. Volik,Christopher J. Ong,Martin Gleave,Colin C. Collins,Yuzhuo Wang
标识
DOI:10.1038/s41417-023-00644-9
摘要
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.
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