Androgen receptor splice variant expression and prostate cancer recurrence after salvage therapy

作者：David J. Konieczkowski, Keisuke Otani, Zoe Guan, Michael Drumm, Yukako Otani, Priscilla Oluwakemi Badusi, Ella Chung, Shulin Wu, Elai Davicioni, Philip J. Saylor, Chin‐Lee Wu, Jason A. Efstathiou, David T. Miyamoto · 发表于：npj Precision Oncology · 年份：2025 · DOI：10.1038/s41698-025-01201-3 · 被引用次数：1 · 研究领域：Prostate Cancer Treatment and Research、Prostate Cancer Diagnosis and Treatment、Cancer-related molecular mechanisms research

Prostate cancer is driven by androgen receptor (AR) signaling, and radiotherapy (RT) with or without androgen deprivation therapy (ADT) offers a second opportunity at cure for men with local or biochemical recurrence after prostatectomy. In the metastatic setting, AR RNA splice variants (ARVs), including ligand-independent AR-V7, modulate ADT response and tumor radiosensitivity. Here, we hypothesized that ARVs in primary prostate cancer may likewise modulate response to subsequent salvage RT+ADT. We performed ultra-deep RNA-seq of the AR transcript pool from prostatectomy specimens from 43 men who later received salvage RT+ADT. Eighty-six percent of patients had detectable ARVs (median 3, range 0-12). Of the thirty-two unique ARVs detected, only AR-V7 (present in 14% of patients) was associated with outcomes after salvage RT+ADT (HR for second biochemical failure, 6.2, 95% CI 2.3-16.5, p=0.0003). These results suggest for the first time that AR-V7 may modulate outcomes for localized in addition to metastatic prostate cancer.