Reply to Ugo De Giorgi, Vincenza Conteduca, and Emanuela Scarpi's Letter to the Editor re: Marzia Del Re, Elisa Biasco, Stefania Crucitta, et al. The Detection of Androgen Receptor Splice Variant 7 in Plasma-derived Exosomal RNA Strongly Predicts Resistance to Hormonal Therapy in Metastatic Prostate Cancer Patients. Eur Urol 2017;71:680–7

We appreciate the discussion of our recent article on the detection of AR-V7 in plasma and its association with resistance to hormonal therapy in metastatic prostate cancer [1]. The authors commented on some of the data presented in our recent study and communicated their perspectives on the clinical utility of androgen receptor (AR) copy number changes and AR mutations (2105T > A [p. L702H] and 2632A > G [p.T878A]) in castration-resistant prostate cancer (CRPC) [2]. The AR p.T878A mutation occurs in the ligand-binding domain (exon 8) of the AR and alters the steroid binding properties of the receptor [3]. The mutated receptor also experiences activation by progestins, and in the setting of the double mutant also harboring p.L702H, another variant occurring in the ligand-binding domain (exon 4), it binds strongly to enzalutamide in an agonistic manner, which may offer one explanation for resistance to antiandrogen therapies.