Cell Cycle Checkpoints, the Androgen Receptor and Prostate Cancer

Cell Cycle Control Team

Section: Cancer Research UK Cancer Therapeutics Unit

Prostate cancer is the leading cause of male cancer death in Europe after lung cancer. Its growth is initially dependent on androgen steroid hormones that bind to and activate the androgen receptor (AR). Deregulation of the AR due to mutation or amplification of the AR gene or mutation of upstream signalling pathways leading to inappropriate activation of the AR, is frequently seen in prostate cancer. Conventional prostate cancer treatment involves androgen ablation therapy, radio- and chemotherapy, depending on the stage of the cancer. Radiotherapy and the majority of chemotherapeutic agents all generate DNA damage leading to the induction of cell cycle checkpoints, but it is not clear whether this affects the function of the AR. Our aim therefore is to investigate if ionising radiation- or chemotherapy-induced DNA damage directly affects AR activity and to determine the mechanisms and signalling pathways involved in such a response. The goal is to identify potential signalling pathways that can be targeted for the development of new prostate cancer treatments. Our studies now show that AR activity is regulated in response to DNA damage and we are currently investigating the mechanism(s) underlying this response.