High-grade serous ovarian cancer (HGSOC): optimizing long-term outcomes in the PARPi era

Better understanding differences in treatment response in patients with high-grade serous ovarian carcinoma treated with PARP inhibitors

High-grade serous ovarian carcinoma (HGSOC) is the most common and lethal type of ovarian cancer. It is usually diagnosed at advanced stages and is unfortunately associated with poor outcomes. 

In recent years, the most promising advance in the treatment of these cancer has been the development of orally administered drugs called PARP inhibitors (PARPi). These drugs have had considerable impact, improving survival and in some cases curing HGSOC. However, not all patients respond to them, even if they have the mutation patterns which generally signify they should, and others without the known pattern for response, who are not expected to be very sensitive to the drug, have dramatic responses. 

To better understand why some patients respond to these therapies while others don’t, a team of pan-Canadian experts will perform an in-depth genomic and clinical investigation of these cancers. Funded through the MOHCCN’s Pan-Canadian Project Program, the team will be led by Drs. Amit Oza and Stephanie Lheureux at the Princess Margaret Cancer Centre in Toronto and will include collaborators in British Columbia and Québec. 

“We are very excited to receive this funding as it will allow us to delve deeply into understanding how and why some people respond or are resistant to treatment, as well as mechanisms at a molecular level that lead to treatment success or failure,” explain Drs. Oza and Lheureux. “It will also open the door to improve our ability to predicting who will benefit or not from treatment, and how to overcome developing resistance.” 

The study will involve close collaboration between expert researchers and clinicians from cancer centres across Canada. These researchers already have a strong history of collaboration and work together as part of a national Network to determine how to improve outcomes in ovarian cancer. This project will solidify these partnerships, bringing these experts together to collect tissue samples from 10 clinical trials which are in progress or recently completed across the country. 

“These samples will not only allow us to collect clinical and genomic data from patients to further our research but will also allow us to include living ovarian cancer models which can help characterize the detailed mechanisms of response and resistance,” say Drs. Oza and Lheureux. “The detailed molecular profiling we can do with this funding will allow deep characterization of molecular changes which will decipher why a patient with ovarian cancer responds or not, and hopefully how to use that information to overcome mechanisms of resistance.” 

In addition to helping support this research, the clinical and genomic data collected through this study will also contribute to the MOHCCN Gold Cohort, which seeks to be the largest and most complete cancer case resource in Canada, made up of genomic and clinical data from 15,000 cancers patients with different backgrounds and cancer types treated in cancer centres across the country. This resource will help researchers and clinicians match genomic data to treatment response, accelerating precision medicine for cancer in Canada, so that one day all cancer patients can receive the right treatment at the right time for their particular cancer, improving survival and quality of life.