Tracking the genomic footprints as predictive features of platinum refractory high-grade serous ovarian cancers

Michael Smith Foundation for Health Research/BC Cancer Foundation Post-Doctoral Fellowship Award

High-grade serous ovarian cancers (HGS) have a low five year survival rates at less than 40 percent. This is partly because of high relapse rates due to resistance to platinum-based therapies, which is the current standard of treatment. Although these therapies are effective at treating the primary tumour, cancers develop resistance to platinum drugs in almost all instances and the tumours recur.

How genomic instabilities evolve in HGS tumours and lead to platinum-resistance is poorly understood, and there are currently no biomarkers that give a reliable prognosis. We seek to identify effective genomic biomarkers for determining which HGS patients will respond more effectively to platinum-based chemotherapy.

This project will build on our research group's recent observations of differences in global genomic patterns between platinum-sensitive and platinum-resistant groups. We will analyze an HGS cohort of seventy cases composed of short- and long-term survivors with five year clinical follow-up data by:

1. Comparing and contrasting the entire DNA sequence of tumours to the patient's normal DNA to identify global patterns of genomic instability
2. Comparing and contrasting genomic profiles from the whole genome of the short-term and long-term survivors
3. Studying diversity via deep-sequencing data of the tumours.

Ultimately, the results of this project and future work could allow for a long-term prognosis and optimized treatments for patients with HGS ovarian cancer.