Identifying New Drugs for the Treatment of Castrate Resistant Prostate Cancer: Targeting the Achilles' Heel of the Androgen Receptor.

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Prostate cancer is second most common cancer in men world wide, with an estimated 1.3 million new cases in 2018. Men with advanced prostate cancer are treated with hormone therapy, drugs that block the action of the androgen receptor. This protein is found inside prostate cells, binds the hormone testosterone and is a key driver of prostate cancer. Drugs which block the actions of testosterone are a mainstay for the treatment of metastatic disease. These drugs reduce the production of testosterone or switch off the activity of the androgen receptor. However, their effectiveness is blunted by the development of drug-resistance leading to 'castrate resistant' disease. While the androgen receptor remains important in advanced disease, there are currently no new targeted therapies available. We aim to develop novel small molecule inhibitors to switch off androgen receptor activity independent of the hormone-binding status. Our ambitious, but achievable aim will target a part of the receptor, essential for function, but not involved in hormone binding. The effectiveness and drug-like properties of candidate small molecule inhibitors which bind specifically to the receptor will be tested for their ability to neutralise the androgen receptor in laboratory models of prostate cancer. This approach has the advantage of targeting all known forms of the receptor, including those with alterations (mutations) associated with castrate resistant disease. This highly innovative approach to prostate cancer treatment, has the potential to significantly improve the outcome for men with advanced disease.