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.

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

Galli L.;Porta C.;
2019-01-01

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/1303466
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