Plasma Androgen Receptor in Prostate Cancer.

Vincenza Conteduca,Stefania Gargiulo,Giorgia Ravaglia,Cristian Lolli,Giuseppe Schepisi,Mario Pulvirenti,Sarah Pia Colangione,Cecilia Menna,Antonino Romeo,Nicole Brighi,Lorena Rossi,Alberto Farolfi,Salvatore Luca Burgio,Ugo De Giorgi,Chiara Casadei,Amelia Altavilla,Giorgia Gurioli

doi:10.3390/cancers11111719

Abstract

The therapeutic landscape of prostate cancer has expanded rapidly over the past 10 years, and there is now an even greater need to understand the biological mechanisms of resistance and to develop noninvasive biomarkers to guide treatment. The androgen receptor (AR) is known to be involved in the pathogenesis and progression of prostate cancer. Recently, highly sensitive next-generation sequencing and PCR-based methods for analyzing androgen receptor gene (AR) copy numbers (CN) and mutations in plasma were established in cell-free DNA (cfDNA) of patients with castration-resistant prostate cancer (CRPC) treated with different drugs. The study of cfDNA holds great promise for improving treatment in CRPC, especially in the advanced stage of the disease. Recent findings showed the significant association of plasma AR aberrations with clinical outcome in CRPC patients treated with AR-directed therapies, whereas no association was observed in patients treated with taxanes. This suggests the potential for using plasma AR as a biomarker for selecting treatment, i.e., hormone therapy or chemotherapy, and the possibility of modulating taxane dose. In recent years, plasma AR status has also been investigated in association with novel agents, such as 177Lu-PSMA radioligand therapy and PARP inhibitors. This review will focus on AR testing in plasma that may have clinical utility for treatment selection in advanced prostate cancer.

Highlights

Prostate cancer is the most frequent cancer in men and the second most common cause of cancer-related death in Western countries [1]
Plasma androgen receptor (AR) gain and high pre-treatment levels of serum and LDH were viewed as independent predictors of progression-free survival (PFS) and overall survival (OS), suggesting the utility of assessing serum chromogranin A (CGA) before starting abiraterone or enzalutamide treatment together with plasma AR status to identify a subgroup of castration-resistant prostate cancer (CRPC) patients who are not likely to respond to AR-directed agents but have no AR aberrations
The first biomarker study evaluated the association between plasma AR and OS/PFS and prostate-specific antigentreatment (PSA) response rate in 163 docetaxel-treated patients, reporting only a significant shorter OS in AR-gained patients (HR = 1.61, 95% confidence intervals (CI) 1.08–2.39, p = 0.018)

Summary

Introduction

Prostate cancer is the most frequent cancer in men and the second most common cause of cancer-related death in Western countries [1]. [7], with little attention prostate cancer decisions (curative treatments or active surveillance) in paid to molecular features, except for some genomic tests using tissue biopsy (Prolaris, OncotypeDx, the setting of localized disease are still based almost exclusively on histological architecture and Decipher) for men withantigen localized prostate and there is early metastasis (Gleason score)available [6], prostate-specific levelscancer [6] and[8,9,10]. Decipher provides information on genome-wide RNA expression for newly diagnosed patients which can be used to predict the risk of metastasis in men with adverse pathology at radical prostatectomy These assays could help to imrpove prognostic risk stratification to aid treatment decisions [10]. In localized primary tumors, we could identify tumors at high-risk of aggressiveness, after which a so comprehensive molecular analysis could help to identify the best therapeutic strategy for eliminating the aggressive subclones in both neoadjuvant and adjuvant settings

Biomarker Tools in Prostate Cancer

Detection of Androgen Receptor in Plasma

Limitations

Findings

Conclusions