Current therapies for locally advanced or metastatic prostate cancer aim to inhibit androgen receptor (AR) activation directly or by depleting androgens via androgen deprivation therapy. However this therapeutic approach eventually fails in ~80% of patients, leading to development of castrate resistant prostate cancer (CRPC). There are currently few therapeutic options available for CRPC with limited prognostic or predictive biomarkers. The aim of the current study was to determine whether AR phosphorylation at serines 81 (pARser81) and 213 (pARser213) could be exploited as biomarkers. Immunohistochemistry of pARser81 and pARser213 was performed on 73 patients with CRPC and protein expression assessed using the weighted histoscore method. The relationship between pARser81, pARser213 and cancer specific time to death from relapse (TTDR) was determined. High pARser81 and high pARser213 expression were associated with decreased TTDR (4.3 years vs 2.6 years, P=0.013 and 4.7 years vs 2.1 years, P=0.000107). Prognostic significance was further increased when AR phosphorylation at both serine residues were considered together with 5 year survival being stratified from 47 to 7% (P=0.000042). Patients with dual low expression had the longest TTDR (5.7 years vs 2.02 years, P=0.000057) when compared to those with dual high expression. On multivariate analysis, dual phosphorylation was independently associated with TTDR (P=0.040) when combined with known clinical parameters. Considering both pARser81 and pARser213 in combination may serve as a prognostic biomarker for CRPC and potential novel therapeutic targets.
Presenting author: Milly J McAllister, Institute of Cancer Sciences, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Garscube Estate, Switchback Road, G12 8QQ, Glasgow, Scotland. Email: firstname.lastname@example.org.