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Updated: Jul 18, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Clinical implications of AR alterations in advanced prostate cancer: A multi-institutional collaboration
Tanya Dorff1, Zeynep Zengin1, Nicholas Henderson2
1City of Hope.
Background:
AR gene alterations can develop in response to pressure of testosterone suppression and androgen receptor targeting agents (ARTA). Despite this, the relevance of these gene alterations in the context of ARTA treatment and clinical outcomes remains unclear.
Methods:
Patients with castration-resistant prostate cancer (CRPC) who had undergone genomic testing and received ARTA treatment were identified in the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) database. Patients were stratified according to the timing of genomic testing relative to the first ARTA treatment (pre-/post-ARTA). Clinical outcomes such as time to progression, PSA response, and overall survival were compared based on alteration types.
Results:
In total, 540 CRPC patients who received ARTA and had tissue-based (n=321) and/or blood-based (n=244) genomic sequencing were identified. Median age was 62 years (range 39-90) at the time of the diagnosis. Majority were White (72.2%) and had metastatic disease (92.6%) at the time of the first ARTA treatment. Pre-ARTA genomic testing was available in 24.8% of the patients, and AR mutations and amplifications were observed in 8.2% and 13.1% of the patients, respectively. Further, time to progression was longer in patients with AR amplifications (25.7 months) compared to those without an AR alteration (9.6 months; p=0.03). In the post-ARTA group (n=406), AR mutations and AR amplifications were observed in 18.5% and 35.7% of the patients, respectively. The most common mutation in post-ARTA group was L702H (9.9%).
Conclusion:
To our knowledge, this is the largest real-world clinicogenomics database-driven study exploring the development of ARalterations and their association with ARTA treatment outcomes. Our study showed that AR amplifications are associated with longer time to progression on first ARTA treatment. Further prospective studies are needed to optimize therapeutic strategies for patients with AR alterations.
Insights
Androgen receptor (AR) gene amplifications in castration-resistant prostate cancer (CRPC) patients are linked to longer progression-free survival during androgen receptor targeting agent (ARTA) therapy. Further research is needed to optimize ARTA treatment strategies for patients with AR alterations.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Androgen receptor (AR) gene alterations can emerge under selective pressure from testosterone suppression and androgen receptor targeting agents (ARTA).
- The clinical significance of these AR alterations concerning ARTA treatment efficacy and patient outcomes remains incompletely understood.
Conclusions:
- This study represents the largest real-world clinicogenomic analysis of AR alterations in CRPC patients undergoing ARTA treatment.
- AR amplifications are associated with improved time to progression during initial ARTA therapy.
- Prospective studies are warranted to refine therapeutic strategies for CRPC patients with specific AR alterations.
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