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AR-V7 detection in plasma-derived exosomal RNA strongly predicts resistance to hormonal therapy in metastatic prostate cancer

Date

09 Oct 2016

Session

Genitourinary tumours, prostate

Presenters

Marzia Del Re

Citation

Annals of Oncology (2016) 27 (6): 243-265. 10.1093/annonc/mdw372

Authors

M. Del Re1, E. Biasco2, S. Crucitta3, L. Derosa2, E. Rofi3, A. Farnesi2, A. Sbrana2, G. Restante1, L. Galli2, A. Falcone2, G. Jenster4, R.H.N. van Schaik5, R. Danesi1

Author affiliations

  • 1 Clinical And Experimental Medicine, University of Pisa, 56126 - Pisa/IT
  • 2 Translational Research And New Technologies In Medicine, University of Pisa, Pisa/IT
  • 3 Clinical And Experimental Medicine, University of Pisa, Pisa/IT
  • 4 Department Of Urology, Erasmus University Medical Center, Rotterdam/NL
  • 5 Department Of Clinical Chemistry, Erasmus University Medical Center, Rotterdam/NL
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Background

The androgen receptor splice variant 7 (AR-V7) is associated with resistance to hormonal therapy in castration resistant prostate cancer (CRPC). Due to the limitations of methods available for AR-V7 analysis, the identification of a reliable detection method may facilitate the use of this biomarker in clinical practice. In order to provide a reliable laboratory approach to AR-V7 assessment, the present study was conducted to: 1) confirm the role of AR-V7 in prediction of resistance to hormonal therapy; 2) develop a new methodological approach to reliably and easily assess AR-V7 by a digital droplet PCR in exosomal-derived RNA from plasma samples and 3) provide new data to address the correlation between exosomal-derived AR-V7 RNA and resistance, being the translation CTC to exosomes not obvious.

Methods

Two ml of plasma samples were collected from 36 CRPC patients before the beginning of second-line hormonal treatment. Exosomes were isolated and RNA extracted for analysis of AR-V7 by digital droplet PCR.

Results

39% of patients were found carriers of the AR-V7 transcript. Twenty-six patients received abiraterone and 10 enzalutamide. The median clinical or radiographic progression free survival was significantly longer in AR-V7 negative compared to positive patients (20 vs 3 months; P 

Conclusions

The present study demonstrates that plasma-derived exosomal RNA is a reliable source of AR-V7 and its detection predicts resistance to anti-hormonal therapy. The method is sensitive, fast and represents a convenient alternative to other potentially more expensive and less sensitive approaches, i.e., circulating tumor cells.

Clinical trial identification

Not applicable

Legal entity responsible for the study

Prof. Romano Danesi

Funding

Academic fundings

Disclosure

All authors have declared no conflicts of interest.

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