Evolutionary determinants of treatment resistant high grade serous ovarian cancer investigated at single cell resolution
Women diagnosed with high grade serous ovarian cancer (HGS) continue to face poor prognosis, with ten-year survival at only 30-40%. Surgical cytoreduction followed by platinum and taxane-based chemotherapy result in clinical remission for a majority of patients. However, up to 80% of patients will suffer relapse because their disease is treatment resistant. Improved outcomes for HGS require both biomarkers of treatment resistance and development of additional treatments targeting tumour cells resistant to first line therapies.
Relapse in HGS is thought to result from the emergence of resistant tumour clones that evolve de-novo or are selected for during treatment. Dr. McPherson will leverage state-of-the-art single cell genome sequencing technologies to study the genomes of treatment naive primary and metastatic HGS samples, in addition to patient derived xenografts subjected to chemotherapeutic agents. His analysis will focus on understanding the genomic changes that confer treatment resistance, and the evolutionary dynamics that produce those changes.
An improved understanding of the mechanisms and dynamics of treatment resistance will result in improved ability to identify patients with relapse potential and provide targeted therapies to improve survival in HGS.