Grant: Operating Grant

It is estimated that more than 100,000 Canadian men are currently living with prostate cancer and that this year almost 25,000 will be newly diagnosed and over 4,000 will die of this disease, making it the most commonly diagnosed non-skin cancer in men and one of the leading causes of cancer-death. If caught early, it is frequently curable by surgical removal of the prostate or by radiation treatment. However, it often recurs with accompanying metastatic spread to bones. This advanced form of the disease is usually managed with treatments referred to as medical castration that prevent the synthesis of androgens like testosterone or obstruct their ability to bind and activate the androgen receptor in the prostate cancer cell. These treatments block the growth promoting effects of androgens and activate cell death processes in the cancer cells. Unfortunately, the cancers eventually become resistant and progress to the lethal, castration-resistant state with an androgen receptor that is now active despite very low levels of circulating androgens. With previous support from CIHR, we have shown that knocking down this androgen receptor using a specific RNA interference approach inhibits this progression and even causes complete regression of some castration-resistant tumours. We have also shown that we can package these RNA interfering molecules into liposomes, inject them into prostate tumour-bearing animals, and see a reduction of prostate tumour growth. Thus, the main objective of this renewal application is to develop better and more efficient ways to deliver these RNA interference molecules for targeting and knocking down the androgen receptor in castration-resistant prostate tumours. We anticipate that the combined strengths and expertise of the Cullis and Rennie labs will continue to perform synergistically to accelerate development of these delivery systems and have a major impact on the survival of men with advanced, castration-resistant prostate cancer.