Grant: Travel Awards - Institute Community Support

Despite decades of intensive clinical research, advanced prostate cancer remains a lethal disease. Research has shown that some prostate tumours are unable to properly repair changes (mutations) to their DNA; these cases are often particularly aggressive, and can rapidly develop resistance to most treatments. However, the inability to repair DNA damage also creates vulnerabilities to specific therapies, as seen by the dramatic response these tumours can have to platinum-based chemotherapy. Moreover, recent findings have shown the efficacy of a new therapy, poly ADP ribose polymerase (PARP) inhibitors, in treating tumours that have non-functional DNA repair. Unfortunately, the disruption of DNA repair in prostate cancer is still poorly understood, and patients that could benefit from specific anticancer medications are often missed, instead managed with conventional, but ultimately ineffective, therapy. My project aims to better characterize DNA repair-deficient prostate tumours; in understanding the molecular and genetic characteristics unique to these aggressive cases, we can better determine which patients might benefit from platinum chemotherapy and PARP inhibition. My preliminary research has identified three genes (BRCA2, ATM, and CDK12) that contribute to DNA repair, but are non-functional in ~15% of patients with advanced prostate cancer. Initial findings suggest that tumours with disruption of these three genes are unique, possessing specific mutations that set them apart from other prostate tumours. In this project, I will use DNA sequencing to determine the frequency of BRCA2, ATM, and CDK12 disruption in a cohort of ~1800 prostate cancer patients. I will then employ computational tools to identify specific combinations of mutations unique to DNA repair-deficient prostate tumours. Findings from my research will readily translate to the clinic, facilitating a more personalized approach for treating men with advanced prostate cancer.