Grant: CIHR Fellowship

Cancer therapy fails when cancer cells evolve resistance during treatment. Understanding the selective pressures that limit this evolution through the course of disease is therefore essential, but has been hampered by the immense complexity of the genetic landscape of cancer. Recent advances in genomic techniques that reconstruct the past evolutionary trajectories of cancer within a patient are, for the first time, now allowing direct tests of the ways that different factors constrain this evolution. In particular, the patient's immune system is now known to be potent factor that can limit cancer progression, and is expected to be a strong selective force shaping tumor evolution. We will couple high-resolution data on anticancer immune responses with genomic reconstructions of cancer evolutionary history to test the ways that patient immunity constrains evolution in high-grade serous ovarian cancer (HGSC) - a highly lethal disease in urgent need of improved treatments. We aim to understand how HGSC genomes evolve in response to pressure from the immune system. This will allow us to predict new targets for immunotherapy, deploy immunotherapy to help limit the evolution of treatment resistance, and delineate the evolutionary potential of individual HGSCs to improve treatment strategies.