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AR-V7 Androgen Receptor Variant as a Predictor of Response to Androgen-receptor Targeting Agents Used to Treat Castration-refractory Metastatic Prostate Cancer


Authors: Büchler Tomáš 1;  Bobek Vladimír 2,3;  Kološtová Katarína 2
Authors‘ workplace: Onkologická klinika 1. LF UK a Thomayerovy nemocnice, Praha 1;  Ústav laboratorní diagnostiky, FN Královské Vinohrady, Praha 2;  III. chirurgická klinika 1. LF UK a FN Motol, Praha 3
Published in: Klin Onkol 2018; 31(1): 9-14
Category: Review
doi: https://doi.org/10.14735/amko20189

Overview

Background:
Several systemic treatment options are currently available for patients with metastatic castration-refractory prostate cancer (mCRPC), including the androgen-receptor targeting agents (ARTA) enzalutamide and abiraterone, the taxanes docetaxel and cabazitaxel, and the radioisotope drug 223-radium dichloride. In some patients with mCRCP, alternative splicing of androgen receptor (AR) mRNA occurs, resulting in the formation of a truncated AR lacking the androgen-binding domain. These receptors activate downstream signalling pathways even without the ligand. Recent studies show that the presence of the AR-V7 (ARV – AR variants) splicing variant is associated with resistance to ARTA. Bec>ause the presence of AR-V7 does not affect the efficacy of other systemic therapies used in mCRCPs, particularly taxanes, AR-V7 is a candidate predictive biomarker for the individualisation of mCRCP treatment. Two types of assays based on mRNA or abnormal protein detection are used to detect AR-V7 in circulating tumour cells.

Aim:
To describe the current status of AR-V7 testing in mCRPC and possible applications of this method for predicting outcomes of ARTA therapy.

Conclusion:
The percentage of CTC AR-V7+ in ARTA-naive men is relatively low at baseline, but in patients pretreated with ARTA, the prevalence of AR-V7 increases to 19–34%. Given the relatively high expected prevalence, AR-V7 testing may be economically feasible in this population. The proportion of AR-V7+ patients responding to ARTA retreatment appears to be very low, at only 4.8%. AR-V7 testing could thus be useful if an ARTA switch is considered in a patient progressing onto an ARTA drug. Both protein-based tests and mRNA-based tests are currently undergoing clinical validation in prospective studies, with results expected within a year.

Key words:
prostate cancer – abiraterone – enzalutamide – alternative splicing – drug resistance

Submitted:
30. 8. 2017

Accepted:
5. 11. 2017

doc. MUDr. Tomáš Büchler, Ph.D. received honorary lectures and publications from Astellas and Janssen and a travel grant from Janssen.

Supported by Ministry of Health, Czech Republic – conceptual development of research organization Thomayer Hospital – TN 0064190.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.


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