Grant: Operating Grant

In North America, bladder cancer is now the fourth most frequently diagnosed cancer in men and significantly increasing among women. Radiation therapy for localized bladder cancer is particularly attractive as it preserves the bladder and allows for urinary and sexual functions; however, it offers 5-year overall survival rates of only 50%. Significant toxicity and lack of local control of disease remains problematic. Furthermore, once distantly metastatic, virtually all bladder cancer patients will succumb to the disease with median survival no better than 18 months even with the best available chemotherapeutic regimens. Hence, there is a desperate need not only to improve efficacy of organ-preserving therapies for clinically localized disease, but also to improve treatment for metastatic bladder cancer. We have previously reported that inhibiting a key signaling pathway (mTOR) has a significant impact on tumor shrinkage and increases the success of radiation therapy in bladder cancer. However, many bladder tumors are aggressive and resistant to radiation despite the addition of mTOR inhibitors. Our proposal is to investigate the mechanism of cancer resistance to the combination of radiation and mTOR inhibition. The aim is to identify molecular signals that correlate with aggressive cancer and more importantly, to identify key biomarkers that help predict response to therapy in order to avoid unnecessary toxicity in patients while prolonging survival in others.