Androgen receptor (AR) splice variant 7 and full-length AR expression is associated with clinical outcome: a translational study in patients with castrate-resistant prostate cancer.

Tytuł:: Androgen receptor (AR) splice variant 7 and full-length AR expression is associated with clinical outcome: a translational study in patients with castrate-resistant prostate cancer.
Autorzy:: Del Re M; Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Crucitta S; Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Sbrana A; Medical Oncology Unit, Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy.
Rofi E; Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Paolieri F; Medical Oncology Unit, Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy.
Gianfilippo G; Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Galli L; Medical Oncology Unit, Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy.
Falcone A; Medical Oncology Unit, Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy.
Morganti R; Section of Statistics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Porta C; Department of Internal Medicine, University of Pavia, Pavia, Italy.; Division of Translational Oncology, I.R.C.C.S. Istituti Clinici Scientifici Maugeri, Pavia, Italy.
Efstathiou E; Division of Cancer Medicine, Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Centre, Houston, TX, USA.
van Schaik R; Department of Clinical Chemistry, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Jenster G; Department of Urology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Danesi R; Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Źródło:: BJU international [BJU Int] 2019 Oct; Vol. 124 (4), pp. 693-700.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Original Publication: Oxford, UK : Blackwell Science, c1999-
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Grant Information:: Fondazione Cassa di Risparmio di Lucca (Lucca, Italy); Sanofi Genzyme
Contributed Indexing:: Keywords: #PCSM; #ProstateCancer; AR-FL; AR-V7; AR-directed therapy; castrate-resistant prostate cancer; predictive biomarkers
Entry Date(s):: Date Created: 20190506 Latest Revision: 20230201
Update Code:: 20240105
DOI:: 10.1111/bju.14792
PMID:: 31055861
: Czasopismo naukowe

Pełny tekst

Objectives: To investigate if full-length androgen receptor (AR-FL) is associated with resistance to androgen receptor (AR)-directed therapy independently and/or combined with AR splice variant 7 (AR-V7).
Patients and Methods: Plasma samples were prospectively collected from 73 patients with castrate-resistant prostate cancer before first- or second-line AR-directed therapy. mRNA was isolated from exosomes and AR-FL and AR-V7 were analysed by droplet digital PCR.
Results: AR-FL was detected in all patients and 22% of them were AR-V7-positive at baseline. AR-FL expression was significantly higher in AR-V7-positive vs AR-V7-negative patients (P < 0.0001). After stratifying patients by tertile for AR-FL expression, progression-free survival (PFS) was 22 vs 18 vs 4 months for lower vs intermediate vs higher tertile, respectively (P = 0.0003). The median PFS and overall survival were significantly longer in AR-V7-negative vs AR-V7-positive patients (20 vs 4 months, P < 0.0001; not reached vs 9 months, P < 0.0001, respectively).
Conclusions: Resistance to AR-directed therapy was associated with the presence of AR-V7; however, AR-FL expression may help better refine response and survival of patients to AR-directed therapy. Both biomarkers, if validated in prospective trials, could be used to select the best treatment strategy.
(© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Comment in: BJU Int. 2019 Oct;124(4):549-550. (PMID: 31908596)

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