In a collaborative study, researchers at the Departments of Urology and Experimental Endocrinology, the Institute of Pathology and the Institute of Human Genetics of the University Medical Center Göttingen (UMG) gained new preclinical data on the treatment of castration-resistant prostate cancer (CRPC).

Advanced prostate cancer can progress to CRPC, and to date no curative treatment exists for CRPC. Targeted therapeutic approaches, e.g. androgen deprivation treatment (ADT) targeting the androgen receptor (AR), initially effect tumor regression, but eventually tumor cells become resistant. One of the key mechanisms contributing to ADT resistance is overexpression of AR and its splice variants (ARVs), which is also present in the human prostate cancer cell line VCaP. In this new study, researchers generated three distinct cell models from the VCaP cell line, analogous to the stages of ADT (1. androgen-sensitive VCaP cells; 2. castration-resistant VCaP cells; 3. VCaP cells treated with abiraterone). Stimulation of estrogen receptor β (ERβ) with its specific agonist 8β-VE2 in these three stages of VCaP cells led to a decrease in tumor cell survival and an increase in apoptosis in a time and dose-dependent manner. Furthermore, 8β-VE2 treatment of the VCaP cells resulted in a reduced expression of AR and its splice variants under maximum ADT.

Taken together, the results of this interdisciplinary study suggest that ERβ-mediated CRPC treatment has advantages (e.g. avoidance of cross resistance) over the AR-targeted therapies currently used.

The results of the study have now been published in Oncotarget:

Prospects of estrogen receptor β activation in the treatment of castration-resistant prostate cancer
Gehrig J, Kaulfuß S, Jarry H, Bremmer F, Stettner M, Burfeind P, Thelen P.
Oncotarget 2017; Advance Publications, doi: 10.18632/oncotarget.16496