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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

2422 - Role of AR-V7 and AR-FL in resistance to hormonal therapy in mCRPC: independent actors or reciprocal drivers? A translational study by Meet-Uro group

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Marzia Del Re

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

M. Del Re1, S. Crucitta2, A. Sbrana3, E. Rofi2, F. Paolieri4, L. Galli5, A. Falcone4, R. van Schaik6, G. Jenster7, R. Morganti3, S. Pignata8, R. Danesi1

Author affiliations

  • 1 Clinical And Experimental Medicine, University of Pisa, 56126 - Pisa/IT
  • 2 Clinical And Experimental Medicine, University of Pisa, 56100 - Pisa/IT
  • 3 Medical Oncology 2 Unit, Azienda Ospedaliera Universitaria S.Chiara, 56100 - Pisa/IT
  • 4 Medical Oncology, Azienda Ospedaliera Universitaria S.Chiara, 56100 - Pisa/IT
  • 5 Uo Oncologia Medica 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana Istituto Toscano Tumori, 56100 - Pisa/IT
  • 6 Clinical Chemistry, Erasmus University, Rotterdam/NL
  • 7 Josephine Nefkens Institute, Erasmus University, Rotterdam/NL
  • 8 Urology And Gynecology, Istituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, 80131 - Napoli/IT
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Resources

Abstract 2422

Background

The androgen receptor splice variant 7 (AR-V7) is strongly associated with resistance to hormonal therapy (HT) in castration-resistant prostate cancer (CRPC), although it is not implemented in clinical practice as a biomarker. The AR-full length (AR-FL) is also overexpressed in CRPC but its role has yet to be clarified. The aim of the present work was to investigate the role of AR-V7 and AR-FL as predictors of resistance to HT in plasma-derived exosomal RNA.

Methods

6 ml of blood were collected in EDTA tubes before the start of abiraterone/enzalutamide; blood was centrifuged and plasma stored at -80 °C until analysis. Exosomes isolation and RNA extraction were performed using the exoRNeasy kit (Qiagen) as per manufacturer instructions. The analysis of AR-FL and AR-V7 were performed by digital droplet PCR using the One-Step RT-ddPCR kit (BioRad). The absolute target concentration as copies/ml in samples was calculated by ddPCR QuantaSoft and statistical analyses were performed by SPSS v.24.

Results

52 patients (pts) were enrolled; AR-FL was detected in all pts (median: 700 copies/ml), while 15 subjects (28.8%) were AR-V7 + (median: 310 copies/ml) at baseline. The amount of AR-FL was significantly higher in pts AR-V7+ vs AR-V7- (6700 vs 490 copies/ml, p < 0.0001). Median PFS and OS were longer in AR-V7- vs AR-V7+ pts (median PFS 25 vs 4 mo, p < 0.0001; median OS 38 vs 9 mo, p < 0.0001). A ROC curve was calculated for AR-FL in the overall population and 950 copies/ml was identified as cut-off value. Pts were then stratified across this value and it was found that PFS was 22 mo in pts with <950 AR-FL copies/ml vs 4 mo in pts with ≥950 copies/ml (p = 0.0003). In 12/15 AR-V7+ pts the AR-FL expression was ≥950 copies/ml while in 3/15 AR-V7+ pts, AR-FL expression was <950 copies/ml; however, their PFS reflected the AR-V7 better than AR-FL status, being, respectively 6, 10, 4 mo. No other clinical variables were correlated with worse PFS at the univariate analysis (i.e. Gleason score ≤7 vs > 7, age).

Conclusions

This study demonstrates that resistance to HT may be predicted by AR-V7, making it a clinically relevant biomarker. AR-FL over-expression may contribute to hormone resistance although AR-V7 plays a primary role.

Clinical trial identification

Legal entity responsible for the study

Romano Danesi.

Funding

University of Pisa.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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