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Open AccessArticle

Analysis of AR/ARV7 Expression in Isolated Circulating Tumor Cells of Patients with Metastatic Castration-Resistant Prostate Cancer (SAKK 08/14 IMPROVE Trial)

1
Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031 Basel, Switzerland
2
Department of Oncology/Hematology, Cantonal Hospital Graubünden, 7000 Chur, Switzerland
3
Department of Oncology, Cantonal Hospital Winterthur, 8401 Winterthur, Switzerland
4
Department of Oncology/Hematology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
5
University of Bern, 3012 Bern, Switzerland
6
Department of Urology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland
7
Swiss Group for Clinical Cancer Research (SAKK) Coordinating Center, 3008 Bern, Switzerland
8
Department of Medical Oncology, Cantonal Hospital Olten, 4600 Olten, Switzerland
9
Clinic of Medical Oncology, Oncology Institute of Southern Switzerland, 6500 Bellinzona, Switzerland
10
Department of Oncology/Hematology, Hospital of Solothurn, 4500 Solothurn, Switzerland
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(8), 1099; https://doi.org/10.3390/cancers11081099
Received: 7 June 2019 / Revised: 12 July 2019 / Accepted: 30 July 2019 / Published: 1 August 2019
(This article belongs to the Special Issue Liquid Biopsy for Cancer)
Despite several treatment options and an initial high response rate to androgen deprivation therapy, the majority of prostate cancers will eventually become castration-resistant in the metastatic stage (mCRPC). Androgen receptor splice variant 7 (ARV7) is one of the best-characterized androgen receptor (AR) variants whose expression in circulating tumor cells (CTCs) has been associated with enzalutamide resistance. ARV7 expression analysis before and during enzalutamide treatment could identify patients requiring alternative systemic therapies. However, a robust test for the assessment of the ARV7 status in patient samples is still missing. Here, we implemented an RT-qPCR-based assay for detection of AR full length (ARFL)/ARV7 expression in CTCs for clinical use. Additionally, as a proof-of-principle, we validated a cohort of 95 mCRPC patients initiating first line treatment with enzalutamide or enzalutamide/metformin within a clinical trial. A total of 95 mCRPC patients were analyzed at baseline of whom 27.3% (26/95) had ARFL+ARV7+, 23.1% (22/95) had ARFL+ARV7−, 23.1% (22/95) had ARFL−ARV7−, and 1.1% (1/95) had ARFL−ARV7+ CTCs. In 11.6% (11/95), no CTCs could be isolated. A total of 25/95 patients had another CTC analysis at progressive disease, of whom 48% (12/25) were ARV7+. Of those, 50% (6/12) were ARV7− and 50% (6/12) were ARV7+ at baseline. Our results show that mRNA analysis of isolated CTCs in mCRPC is feasible and allows for longitudinal endocrine agent response monitoring and hence could contribute to treatment optimization in mCRPC. View Full-Text
Keywords: mCRPC; circulating tumor cells; liquid biopsy; androgen receptor; ARV7 mCRPC; circulating tumor cells; liquid biopsy; androgen receptor; ARV7
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Bratic Hench, I.; Cathomas, R.; Costa, L.; Fischer, N.; Gillessen, S.; Hench, J.; Hermanns, T.; Kremer, E.; Mingrone, W.; Pereira Mestre, R.; Püschel, H.; Rothermundt, C.; Ruiz, C.; Tolnay, M.; Von Burg, P.; Bubendorf, L.; Vlajnic, T. Analysis of AR/ARV7 Expression in Isolated Circulating Tumor Cells of Patients with Metastatic Castration-Resistant Prostate Cancer (SAKK 08/14 IMPROVE Trial). Cancers 2019, 11, 1099.

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