Androgen receptor expression in circulating tumour cells from castration-resistant prostate cancer patients treated with novel endocrine agents.
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Authors
Crespo, M
van Dalum, G
Ferraldeschi, R
Zafeiriou, Z
Sideris, S
Lorente, D
Bianchini, D
Rodrigues, DN
Riisnaes, R
Miranda, S
Figueiredo, I
Flohr, P
Nowakowska, K
de Bono, JS
Terstappen, LWMM
Attard, G
van Dalum, G
Ferraldeschi, R
Zafeiriou, Z
Sideris, S
Lorente, D
Bianchini, D
Rodrigues, DN
Riisnaes, R
Miranda, S
Figueiredo, I
Flohr, P
Nowakowska, K
de Bono, JS
Terstappen, LWMM
Attard, G
Document Type
Journal Article
Date
2015-03-31
Date Accepted
2015-01-27
Abstract
BACKGROUND: Abiraterone and enzalutamide are novel endocrine treatments that abrogate androgen receptor (AR) signalling in castration-resistant prostate cancer (CRPC). Here, we developed a circulating tumour cells (CTCs)-based assay to evaluate AR expression in real-time in CRPC and investigated nuclear AR expression in CTCs in patients treated with enzalutamide and abiraterone. METHODS: CTCs were captured and characterised using the CellSearch system. An automated algorithm to identify CTCs and quantify AR expression was employed. The primary aim was to evaluate the association between CTC AR expression and prior treatment with abiraterone or enzalutamide. RESULTS: AR expression in CTCs was evaluated in 94 samples from 48 metastatic CRPC patients. We observed large intra-patient heterogeneity of AR expression in CTCs. Prior exposure to abiraterone or enzalutamide was not associated with a change in CTCs AR expression (median intensity and distribution of AR-positive classes). In support of this, we also confirmed maintained nuclear AR expression in tissue samples collected after progression on abiraterone. AR staining also identified additional AR-positive CD45-negative circulating cells that were CK-negative/weak and therefore missed using standard protocols. The number of these events correlated with traditional CTCs and was associated with worse outcome on univariate analysis. CONCLUSIONS: We developed a non-invasive method to monitor AR nuclear expression in CTCs. Our studies confirm nuclear AR expression in CRPC patients progressing on novel endocrine treatments. Owing to the significant heterogeneity of AR expression in CTCs, studies in larger cohorts of patients are required to identify associations with outcome.
Citation
British journal of cancer, 2015, 112 (7), pp. 1166 - 1174
Source Title
Publisher
NATURE PUBLISHING GROUP
ISSN
0007-0920
eISSN
1532-1827
Research Team
Cancer Biomarkers
Prostate Cancer Targeted Therapy Group
Treatment Resistance
Prostate Cancer Targeted Therapy Group
Treatment Resistance