OBJECTIVES: To compare the performance of two established androgen receptor splice variant 7 (AR-V7) mRNA detection systems, as paradoxical responses to next-generation androgen-deprivation therapy in AR-V7 mRNA-positive circulating tumour cells (CTC) of patients with castration-resistant prostate cancer (CRPC) could be related to false-positive classification using detection systems with different sensitivities. MATERIALS AND METHODS: We compared the performance of two established mRNA-based AR-V7 detection technologies using either SYBR Green or TaqMan chemistries. We assessed in vitro performance using eight genitourinary cancer cell lines and serial dilutions in three AR-V7-positive prostate cancer cell lines, as well as in 32 blood samples from patients with CRPC. RESULTS: Both assays performed identically in the cell lines and serial dilutions showed identical diagnostic thresholds. Performance comparison in 32 clinical patient samples showed perfect concordance between the assays. In particular, both assays determined AR-V7 mRNA-positive CTCs in three patients with unexpected responses to next-generation anti-androgen therapy. Thus, technical differences between the assays can be excluded as the underlying reason for the unexpected responses to next-generation anti-androgen therapy in a subset of AR-V7 patients. CONCLUSIONS: Irrespective of the method used, patients with AR-V7 mRNA-positive CRPC should not be systematically precluded from an otherwise safe treatment option.
OBJECTIVES: To compare the performance of two established androgen receptor splice variant 7 (AR-V7) mRNA detection systems, as paradoxical responses to next-generation androgen-deprivation therapy in AR-V7 mRNA-positive circulating tumour cells (CTC) of patients with castration-resistant prostate cancer (CRPC) could be related to false-positive classification using detection systems with different sensitivities. MATERIALS AND METHODS: We compared the performance of two established mRNA-based AR-V7 detection technologies using either SYBR Green or TaqMan chemistries. We assessed in vitro performance using eight genitourinary cancer cell lines and serial dilutions in three AR-V7-positive prostate cancer cell lines, as well as in 32 blood samples from patients with CRPC. RESULTS: Both assays performed identically in the cell lines and serial dilutions showed identical diagnostic thresholds. Performance comparison in 32 clinical patient samples showed perfect concordance between the assays. In particular, both assays determined AR-V7 mRNA-positive CTCs in three patients with unexpected responses to next-generation anti-androgen therapy. Thus, technical differences between the assays can be excluded as the underlying reason for the unexpected responses to next-generation anti-androgen therapy in a subset of AR-V7 patients. CONCLUSIONS: Irrespective of the method used, patients with AR-V7 mRNA-positive CRPC should not be systematically precluded from an otherwise safe treatment option.
Authors: Emmanuelle Hodara; Gareth Morrison; Alexander Cunha; Daniel Zainfeld; Tong Xu; Yucheng Xu; Paul W Dempsey; Paul C Pagano; Farideh Bischoff; Aditi Khurana; Samuel Koo; Marc Ting; Philip D Cotter; Mathew W Moore; Shelly Gunn; Joshua Usher; Shahrooz Rabizadeh; Peter Danenberg; Kathleen Danenberg; John Carpten; Tanya Dorff; David Quinn; Amir Goldkorn Journal: JCI Insight Date: 2019-03-07
Authors: Irfan Asangani; Ian A Blair; Gregory Van Duyne; Vincent J Hilser; Vera Moiseenkova-Bell; Stephen Plymate; Cynthia Sprenger; A Joshua Wand; Trevor M Penning Journal: J Biol Chem Date: 2021-01-09 Impact factor: 5.157