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. Overall design: RNA sequencing of metastases from individuals with castration resistant prostate cancer (CRPC) using Illumina HiSeq 2500.

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Sharp A, Coleman I, Yuan W, Sprenger C, Dolling D, Rodrigues DN, Russo JW, Figueiredo I, Bertan C, Seed G, Riisnaes R, Uo T, Neeb A, Welti J, Morrissey C, Carreira S, Luo J, Nelson PS, Balk SP, True LD, de Bono JS, Plymate SR