Grant: Project Grant

Bladder cancer is the 5th most common cancer affecting Canadians. There are notable differences in the incidence between sexes, with bladder cancer four times more common in men, though tumors in women tend to be more aggressive. However, the reasons why these differences between sexes exist remain poorly understood. There is a need to understand how biologic differences such as sex hormones impact bladder cancer and to understand how these differences may be harnessed to improve treatment responses. Superficial bladder tumors represent approximately 75% of all bladder tumors and have a high and costly recurrence rate. Immunotherapy using a vaccine for tuberculosis called Bacille-Calmette Guérin(BCG) remains the standard treatment, unchanged for over 40 years. We and others observed that treatments which target hormone biology can decrease tumor recurrences of superficial bladder tumors. Our research investigates how current treatments modulating androgens or estrogens may be repurposed to treat bladder cancer patients. First, clinical trials of anti-androgens or supplemental estrogens in combination with BCG treatment for superficial bladder cancer will provide the needed evidence for further clinical studies in men and women, respectively. Second, we will use laboratory models to investigate the mechanisms of how anti-androgen therapy and sex hormones may alter immune cells' function and anti-cancer activity. Our research will provide a pathway forward to improving the current practice for superficial bladder cancer which is essentially unchanged for many decades. The integration of patient samples collected in the clinical trial with laboratory experiments will expand our understanding of the reasons for sex differences in bladder cancer and support further practice-changing clinical trials. Thus, our results will help improve outcomes for bladder cancer patients but may also provide knowledge which applies to other cancers where immunotherapy is effective.