High-Throughput Screening Assay Identifies Drugs to Treat Resistant Prostate Cancer

Many men with prostate cancer receive hormone treatment, which works by stopping male hormones like testosterone feeding the cancer. The problem is that some cancers become resistant to hormone treatment. Male hormones help prostate cancer to grow and spread by attaching to proteins called androgen receptors (AR). When these hormones attach to the AR, it is like they switch the AR on. Many prostate cancer drugs work by attaching to the AR, physically blocking hormones from being able to switch it on. In some men, the AR itself changes, so that it’s always switched on, and it’s missing the part that drugs normally attach to. Now, a novel high-throughput screening assay has been designed to identify inhibitors of the androgen receptor and could be used to identify new drugs to treat resistant forms of prostate cancer.

The cell-based high-throughput assay for screening and identifying inhibitors of the AR-NTD has been developed by researchers at the University of Aberdeen (Aberdeen, Scotland). Approximately 75% of patients with castrate resistant prostate cancer express AR variants that lack the ligand binding domain. These forms of disease evade all forms of currently available AR-targeting treatment. The amino terminal domain (NTD) of the AR has been shown to be critical for the receptor’s function.

“We demonstrate the suitability of the assay for high-throughput screening platforms and validate two initial hits emerging from a small, targeted, library screen in prostate cancer cells,” stated the investigators.

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University of Aberdeen 

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