Kantonsspital St.Gallen
login

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

Ivana Bratic Hench, Richard Cathomas, Luigi Costa, Natalie Fischer, Silke Gillessen Sommer, Jürgen Hench, Thomas Hermanns, Eloïse Kremer, Walter Mingrone, Ricardo Pereira Mestre, Heike Püschel, Christian Rothermundt, Christian Ruiz, Markus Tolnay, Philippe Von Burg, Lukas Bubendorf, Tatjana Vlajnic & Swiss Group For Clinical Cancer Research Sakk

abstract 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.
   
citation Hench I B, Cathomas R, Costa L, Fischer N, Gillessen Sommer S, Hench J, Hermanns T, Kremer E, Mingrone W, Mestre R P, Püschel H, Rothermundt C, Ruiz C, Tolnay M, Burg P V, Bubendorf L, Vlajnic T, Sakk S G F C C R. Analysis of AR/ARV7 Expression in Isolated Circulating Tumor Cells of Patients with Metastatic Castration-Resistant Prostate Cancer (SAKK 08/14 IMPROVE Trial). Cancers (Basel) 2019; 11:.
   
type journal paper/review (English)
date of publishing 01-08-2019
journal title Cancers (Basel) (11/8)
ISSN print 2072-6694
PubMed 31374981
DOI 10.3390/cancers11081099