Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Bladder cancer is the fourth most common male cancer. Approximately 70% of bladder cancers are non-muscle invasive at initial diagnosis but up to 80% of patients with superficial bladder cancer will develop recurrent tumours, of which 20-30% progress into more aggressive and potentially lethal tumours. Current treatment with Bacillus Calmette-Guérin (BCG) has shown significant benefits to prevent progression compared to chemotherapeutics but may be associated with significant side effects and high-risk patients ultimately require cystectomy within 15 years. Therefore,new therapies for early-stage high-risk bladder cancer are clearly required to prevent both recurrence and progression. There is growing evidence that many solid tumours of various origins may arise through differentiation from cancer stem cells (CSCs). Although CSCs account for approximately 10% of total tumour cells, they have the ability to replenish all tumour cell types, establish new tumours at distant sites and evade conventional drug therapies. We propose to look at the Sonic Hedgehog (SHH) pathway which we have shown can slow cancer growth and increase sensitivity to chemotherapies. Firstly, we will create cultured cell lines from patient's healthy and cancer tissues and identify the stem cells within. Secondly we will isolate these cells and analyze the gene expression and protein changes that occur in cancer cells. Thirdly, we will interfere with the SHH pathway and examine the effect on stem cell growth in combination with chemotherapy. We expect that the SSH pathway is important to CSCs and that it is a potential target for new therapies. This study will be the first to examine SHH in bladder cancer stem cells.