Grant: Project Grant

The standard of care therapies for advanced prostate cancer, abiraterone and enzalutamide, are not effective in 20-40% of patients. We currently are unable to recognize this subset of patients up-front, which means they are inevitably treated with a drug that will not work: leading to unnecessary treatment side-effects to the patient and wasted time while their disease worsens. Our unique research team combines cancer bioinformatics expertise with clinical oncology to develop genomic-based strategies that better recognize patients with poor prognoses. Although it has long been known that cancers shed a small amount of their DNA into the bloodstream (known as circulating tumor DNA, ctDNA), the analysis of this DNA is only now possible through advancement of next-generation sequencing technology. Our recent work has shown that changes detected in ctDNA accurately reflect cancer itself and can therefore show the DNA changes occurring in a patient's prostate cancer before, during, and after treatment. In this project we will look at changes occurring in the ctDNA of hundreds of Canadian men with prostate cancer that are being treated with abiraterone, enzalutamide and other therapies. We will determine which changes can predict a patient's subsequent response to treatment. We are uniquely placed to perform this analysis given our strong track record of success in prostate cancer ctDNA profiling, our novel custom (and validated) methodology, and our recent establishment of a province-wide ctDNA profiling program that has rapidly accrued hundreds of patient blood samples. Success with our project will help us understand why some cancers are intrinsically resistant to the most commonly used therapies. Furthermore, we will have developed a clinically-practical framework (requiring only a blood sample, rather than a metastatic tissue biopsy) that may ultimately help prioritize patients for other therapies that have an improved chance of success.