Marzia Del Re1, Stefania Crucitta1, Andrea Sbrana2, Eleonora Rofi1, Federico Paolieri2, Giulia Gianfilippo1, Luca Galli2, Alfredo Falcone2, Riccardo Morganti3, Camillo Porta4,5, Eleni Efstathiou6, Ron van Schaik7, Guido Jenster8, Romano Danesi1. 1. Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. 2. Medical Oncology Unit, Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy. 3. Section of Statistics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. 4. Department of Internal Medicine, University of Pavia, Pavia, Italy. 5. Division of Translational Oncology, I.R.C.C.S. Istituti Clinici Scientifici Maugeri, Pavia, Italy. 6. Division of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. 7. Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands. 8. Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Abstract
OBJECTIVES: To investigate if full-length androgen receptor (AR-FL) is associated with resistance to 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 CRPC before first or second-line AR-directed therapy. mRNA was isolated from exosomes and AR-FL and AR-V7 were analyzed by ddPCR. RESULTS: AR-FL was detected in all patients while 22% were AR-V7+ at baseline. AR-FL expression was significantly higher in AR-V7+ vs AR-V7- patients (p<0.0001). Stratifying patients by tertiles for AR-FL expression, PFS was 22 vs 18 vs 4 months for lower vs intermediate vs higher tertile, respectively (p=0.0003). Median PFS and OS were significantly longer in AR-V7- vs AR-V7+ patients (20 vs 4 months, p<0.0001; not reached vs 9 months, p<0.0001, respectively). CONCLUSIONS: Resistance to AR-directed therapy is 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, may be used to select the best treatment strategy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
OBJECTIVES: To investigate if full-length androgen receptor (AR-FL) is associated with resistance to 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 CRPC before first or second-line AR-directed therapy. mRNA was isolated from exosomes and AR-FL and AR-V7 were analyzed by ddPCR. RESULTS:AR-FL was detected in all patients while 22% were AR-V7+ at baseline. AR-FL expression was significantly higher in AR-V7+ vs AR-V7- patients (p<0.0001). Stratifying patients by tertiles for AR-FL expression, PFS was 22 vs 18 vs 4 months for lower vs intermediate vs higher tertile, respectively (p=0.0003). Median PFS and OS were significantly longer in AR-V7- vs AR-V7+ patients (20 vs 4 months, p<0.0001; not reached vs 9 months, p<0.0001, respectively). CONCLUSIONS: Resistance to AR-directed therapy is 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, may be used to select the best treatment strategy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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