Heterogeneity of Androgen Receptor Splice Variant-7 (AR-V7) Protein Expression and Response to Therapy in Castration Resistant Prostate Cancer (CRPC)

Liquid biopsies have demonstrated that the constitutively active androgen receptor splice variant-7 (AR-V7) associates with reduced response and overall survival (OS) from endocrine therapies in castration resistant prostate cancer (CRPC). However, these studies provide little information pertaining to AR-V7 biology and expression in prostate cancer (PC) tissue. Following generation and validation of a novel AR-V7 antibody for immunohistochemistry (IHC); nuclear AR-V7 protein expression was determined for 358 primary prostate samples (358 patients) and 293 metastatic biopsies (194 patients). Associations with disease progression, nuclear AR full length (AR-FL) expression, response to abiraterone and/or enzalutamide, and gene signatures (from three independent cohorts) was determined. RNA sequencing of metastases from individuals with castration resistant prostate cancer (CRPC) using Illumina HiSeq 2500.