Detection of AR-V7 transcripts in whole blood RNA of patients with metastatic castration-resistant prostate cancer (MCRPC).

Background: The expression of androgen receptor splice variant 7 (AR-V7) in circulating tumour cells (CTCs) of mCRPC patients potentially confers treatment resistance to AR-axis targeting agents. However, detecting such variants in CTCs is not without difficulties, with high costs of CTC platforms, coupled with the need to enrich patient samples prior to analysis. Our aim was to develop a rapid and sensitive assay for AR-V7 detection in patient whole blood samples. Method(s): Patient samples were obtained as part of the Australia Prostate Biomarker Alliance project. We created and optimised a sensitive, whole blood quantitative real-time polymerase chain reaction assay to correlate outcomes of abiraterone acetate (abiraterone) and enzalutamide-treated patients with expression of AR-V7. The expression of AR-V7 mRNA in whole blood from 19 patients with mCRPC was obtained prior to commencing therapy. Each sample was analysed in triplicate; positivity was defined as at least two results reaching cycle threshold, with a standard deviation of <= 0.25. Gene expression was correlated with PSA response rate using chi-square test. Result(s): In our cohort, 5 of 19 patients (26%) were AR-V7+. Of patients commencing abiraterone or enzalutamide (15/19 patients, 79%),we observed lower PSA response rates in the AR-V7+ (1/4) patients, compared to the ARV7- (8/11) patients (25% vs 73%, P = 0.23). AR-V7 was not detected in any of the 12 normal male controls. Conclusion(s): We demonstrate the development of a sensitive and specific assay for AR-V7 detection in whole blood from mCRPC patients. A modest trend towards lower PSA response rates was seen in AR-V7+ patients compared to AR-V7- patients, in keeping with previous evidence supporting the role of AR variants in resistance to therapies targeting the AR ligand-binding domain. Future directions will include further cohort expansion, and interrogation of other AR variants.