Androgen Receptor Modulation in Prostate Cancer
Basics, Concepts, Methods
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There is considerable evidence to suggest that progression of prostate cancers to castration- resistant is due to inappropriate activation of the androgen receptor (AR) and hence, the AR is a good target for the treatment of this disease. In this study we used two approaches to investigate AR activation and inhibition. We developed high-throughput, non-invasive, cell- based screening assays to rapidly and biologically assess factors that modulate prostate cancer growth and affect AR activity. Using these assays, we found that differentiated osteoblast-like condition media enhanced prostate can...
There is considerable evidence to suggest that progression of prostate cancers to castration- resistant is due to inappropriate activation of the androgen receptor (AR) and hence, the AR is a good target for the treatment of this disease. In this study we used two approaches to investigate AR activation and inhibition. We developed high-throughput, non-invasive, cell- based screening assays to rapidly and biologically assess factors that modulate prostate cancer growth and affect AR activity. Using these assays, we found that differentiated osteoblast-like condition media enhanced prostate cancer cell growth, but not AR activity. In addition, we applied this system to screen compounds, selected through in silico approaches against a crucial pocket on the AR protein. The application of our in silico tools and our cell based screening assay resulted in identification of 17 compounds out of 4 millions that can inhibit AR activity. Importantly, some of these compounds are more potentthan bicalutamide, which is one of the most potent antiandrogen drugs currently used to treat patients with metastatic prostate cancer.
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