Purpose
Reliable molecular diagnostic tools are still unavailable for making informed treatment decisions and monitoring the response in castration resistant prostate cancer (CRPC) patients. In this study we evaluated the significance of whole blood-circulating androgen receptor (AR) transcripts of full length (AR-FL) and splice variants (AR-Vs: AR-V1, -V3, and -V7) as biomarkers of abiraterone acetate (AA) treatment resistance in CRPC patients.
Materials and Methods
After retrospective analysis in 112 prostate specimens, AR-FL, -V1, -V3, and -V7 were evaluated in 185 serial blood samples, prospectively collected from 102 CRPC patients before and during AA therapy via reverse transcription quantitative PCR.
Results
AR-FL was present in all samples while AR-V1, -V3, -V7, and at least one of them was detected in 17%, 55%, 65%, and 81% of CRPC blood samples, respectively. The highest amount of AR-V1 was found in patients’ blood whose response time was short and medium in comparison to extended. Patients having a higher level of AR-FL and/or AR-V1 had the shortest PFS and OS (P<0.0001).
Conclusions
Blood-circulating AR-FL or -V1 can serve as blood-based biomarkers for identification of the primary resistance to AA and the tool to monitor de novo resistance development during AA treatment.