Publication
Analysis of AR/ARV7 Expression in Isolated Circulating Tumor Cells of Patients with Metastatic Castration-Resistant Prostate Cancer (SAKK 08/14 IMPROVE Trial)
Journal Paper/Review - Aug 1, 2019
Hench Ivana Bratic, Vlajnic Tatjana, Bubendorf Lukas, Burg Philippe Von, Tolnay Markus, Ruiz Christian, Rothermundt Christian, Püschel Heike, Mestre Ricardo Pereira, Mingrone Walter, Kremer Eloïse, Hermanns Thomas, Hench Jürgen, Gillessen Sommer Silke, Fischer Natalie, Costa Luigi, Cathomas Richard, Sakk Swiss Group For Clinical Cancer Research
Units
PubMed
Doi
Citation
Type
Journal
Publication Date
Issn Print
Brief description/objective
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.