Grant: Early Career Investigator Awards - Urothelial Cancer

Metastatic bladder cancer is a lethal and under-studied disease. Chemotherapy has historically been the most effective treatment for metastatic disease, but long-term survival has been a rarity. Recently, new drugs including immunotherapies are showing significant promise, but only a small proportion of patients respond to these treatments and we have no reliable way of predicting who the responders will be. During the first three years of my faculty appointment I have worked closely with clinical collaborators to develop a blood test that can identify tumour DNA present in a small blood sample (called circulating tumuor DNA, ctDNA). We can therefore use ctDNA to evaluate the genetic changes (mutations) in metastatic cancers that correspond to treatment response or resistance. Our preliminary work suggests that mutations detected in ctDNA accurately reflect cancer itself, meaning that we can profile a patient's metastatic bladder cancer before treatment without the need for a tissue biopsy. In this project we will identify mutations in the ctDNA of hundreds of Canadians with metastatic bladder cancer that are being treated with chemotherapy or immunotherapy. My research team will determine which mutations can predict a patient's subsequent response to treatment using our rare combination of cancer bioinformatics and clinical oncology. We are uniquely placed to perform this analysis given our strong track record of success in metastatic cancer ctDNA profiling, our novel custom methodology, and our recent establishment of a province-wide ctDNA profiling program that is rapidly accruing hundreds of patient blood samples. Success with our project will help explain why some metastatic bladder cancers are intrinsically responsive or resistant to the most commonly used therapies. Furthermore, we will have developed a clinically-practical framework (requiring only a blood sample) that may ultimately help prioritize patients for therapies with the best chance of success.