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Analysis of AR-FL and AR-V1 in Whole Blood of Patients with Castration Resistant Prostate Cancer as a Tool for Predicting Response to Abiraterone Acetate

Stuopelyte, Kristina ; Sabaliauskaite, Rasa ; Bakavicius, Arnas ; Haflidadóttir, Benedikta S. LU ; Visakorpi, Tapio ; Väänänen, Riina Minna ; Patel, Chintan ; Danila, Daniel C. ; Lilja, Hans LU orcid and Lazutka, Juozas R. , et al. (2020) In The Journal of urology 204(1). p.71-78
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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
abiraterone acetate, androgen, castration-resistant, drug resistance, liquid biopsy, neoplasm, prostatic neoplasms, receptors
in
The Journal of urology
volume
204
issue
1
pages
8 pages
publisher
Lippincott Williams & Wilkins
external identifiers
  • pmid:32068491
  • scopus:85086346118
ISSN
1527-3792
DOI
10.1097/JU.0000000000000803
language
English
LU publication?
yes
id
359ecd6c-8377-4e96-873d-87103cc8e06e
date added to LUP
2020-07-02 12:30:18
date last changed
2024-03-04 22:08:09
@article{359ecd6c-8377-4e96-873d-87103cc8e06e,
  abstract     = {{<p>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 &lt;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.</p>}},
  author       = {{Stuopelyte, Kristina and Sabaliauskaite, Rasa and Bakavicius, Arnas and Haflidadóttir, Benedikta S. and Visakorpi, Tapio and Väänänen, Riina Minna and Patel, Chintan and Danila, Daniel C. and Lilja, Hans and Lazutka, Juozas R. and Ulys, Albertas and Jankevicius, Feliksas and Jarmalaite, Sonata}},
  issn         = {{1527-3792}},
  keywords     = {{abiraterone acetate; androgen; castration-resistant; drug resistance; liquid biopsy; neoplasm; prostatic neoplasms; receptors}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{71--78}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{The Journal of urology}},
  title        = {{Analysis of AR-FL and AR-V1 in Whole Blood of Patients with Castration Resistant Prostate Cancer as a Tool for Predicting Response to Abiraterone Acetate}},
  url          = {{http://dx.doi.org/10.1097/JU.0000000000000803}},
  doi          = {{10.1097/JU.0000000000000803}},
  volume       = {{204}},
  year         = {{2020}},
}