Kristina Stuopelyte1,2, Rasa Sabaliauskaite2, Arnas Bakavicius3,2,4, Benedikta S Haflidadóttir5,6, Tapio Visakorpi5,6, Riina-Minna Väänänen7, Chintan Patel8, Daniel C Danila8,9, Hans Lilja8,10,11,12, Juozas R Lazutka1, Albertas Ulys2, Feliksas Jankevicius2,4, Sonata Jarmalaite1,2. 1. Institute of Biomedical Sciences, Life Sciences Center, Vilnius University, Vilnius, Lithuania. 2. National Cancer Institute, Vilnius, Lithuania. 3. Urology Centre, Vilnius University, Vilnius, Lithuania. 4. Faculty of Medicine, Vilnius University, Vilnius, Lithuania. 5. Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. 6. Fimlab Laboratories, Tampere University Hospital, Tampere, Finland. 7. Department of Biotechnology, University of Turku, Turku, Finland. 8. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. 9. Department of Medicine, Weill Cornell Medical College, New York, New York. 10. Department of Surgery (Urology Service), Memorial Sloan Kettering Cancer Center, New York, New York. 11. Department of Translational Medicine, Lund University, Malmö, Sweden. 12. Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
Abstract
PURPOSE: Reliable molecular diagnostic tools are still unavailable for making informed treatment decisions and monitoring the response in patients with castration resistant prostate cancer. We evaluated the significance of whole blood circulating androgen receptor transcripts of full length (AR-FL) and splice variants (AR-V1, AR-V3 and AR-V7) as biomarkers of abiraterone acetate treatment resistance in patients with castration resistant prostate cancer. MATERIALS AND METHODS: After retrospective analysis in 112 prostate specimens AR-FL, AR-V1, AR-V3 and AR-V7 were evaluated in 185 serial blood samples, prospectively collected from 102 patients with castration resistant prostate cancer before and during abiraterone acetate therapy via reverse transcription quantitative polymerase chain reaction. RESULTS: AR-FL was present in all samples while AR-V1, AR-V3, AR-V7 and at least 1 of them was detected in 17%, 55%, 65% and 81% of castration resistant prostate cancer blood samples, respectively. The highest amount of AR-V1 was found in blood of patients whose response time was short and medium in comparison to extended. Patients with a higher level of AR-FL and/or AR-V1 had the shortest progression-free survival and overall survival (p <0.0001). CONCLUSIONS: Blood circulating AR-FL or AR-V1 can serve as blood based biomarkers for identification of the primary resistance to abiraterone acetate and the tool to monitor de novo resistance development during abiraterone acetate treatment.
PURPOSE: Reliable molecular diagnostic tools are still unavailable for making informed treatment decisions and monitoring the response in patients with castration resistant prostate cancer. We evaluated the significance of whole blood circulating androgen receptor transcripts of full length (AR-FL) and splice variants (AR-V1, AR-V3 and AR-V7) as biomarkers of abiraterone acetate treatment resistance in patients with castration resistant prostate cancer. MATERIALS AND METHODS: After retrospective analysis in 112 prostate specimens AR-FL, AR-V1, AR-V3 and AR-V7 were evaluated in 185 serial blood samples, prospectively collected from 102 patients with castration resistant prostate cancer before and during abiraterone acetate therapy via reverse transcription quantitative polymerase chain reaction. RESULTS:AR-FL was present in all samples while AR-V1, AR-V3, AR-V7 and at least 1 of them was detected in 17%, 55%, 65% and 81% of castration resistant prostate cancer blood samples, respectively. The highest amount of AR-V1 was found in blood of patients whose response time was short and medium in comparison to extended. Patients with a higher level of AR-FL and/or AR-V1 had the shortest progression-free survival and overall survival (p <0.0001). CONCLUSIONS: Blood circulating AR-FL or AR-V1 can serve as blood based biomarkers for identification of the primary resistance to abiraterone acetate and the tool to monitor de novo resistance development during abiraterone acetate treatment.
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