Ovarian cancers are the deadliest type of gynecological cancers, with a five-year survival rate of only 45 per cent. To improve outcomes for patients diagnosed with this disease, since 2009, the TFRI has funded the Canadian Ovarian Experimental Unified Resource (COEUR), a pan-Canadian biobank that has helped collect more than 2,000 ovarian cancer samples from patients across the country. This resource has allowed researchers to analyze and compare tumours to identify biomarkers and classify different subtypes of the disease, with the goal of making findings that can help personalize treatments for ovarian cancer patients from coast to coast to coast.
“Since the beginning of the project, our goal has been to create a cohort of patients who have had ovarian cancer and to collect their biological samples so we can ask questions about sub-typing the disease,” explains Dr. Anne-Marie Mes-Masson, a principal scientist at the Centre de recherche du Centre hospitalier de L’Université de Montréal (CRCHUM) and one of three co-principal investigators of COEUR. “This has helped us to identify biomarkers that could allow us to better stratify patients when it comes to treatment.”
Twelve years after it first received TFRI funding, the resource continues to be invaluable for researchers. In recent months, Dr. Mes-Masson and colleagues across the country have used it to make significant findings that could help personalize treatments for patients diagnosed with ovarian cancer.
Discovering new prognostic biomarkers for the deadliest type of ovarian cancer
High-grade serous carcinoma (HGSC) is the most frequent, aggressive, and lethal type of ovarian cancer. Today, standard treatment consists of an aggressive combination of surgery and chemotherapy, with mixed results: while the majority of patients benefit from these invasive treatments, many relapse after only a short period of remission.
In this context, finding prognostic biomarkers that can identify those most likely to survive longer can be useful in the context of clinical management of the disease. That is exactly why Dr. Mes-Masson and her colleagues are so excited about a new discovery published in the International Journal of Molecular Sciences (May 2021).
“We found that searching for two biomarkers that are routinely used in pathology, Keratin 7 and E-Cadherin, is an extremely efficient way to predict patients with the best and worst outcomes,” says Dr. Mes-Masson. “This combination outperforms any other published prognostic biomarker, which is especially helpful as these stainings are routine which means they could be readily taken up by pathologists.”
“The COEUR resource has been instrumental in this work as it provided us with a significant number of high-quality patient tissues and clinical data to get strong and valuable results,” says Dr. Laudine Communal, a clinical coordinator at CRCHUM and the study’s first author. “We believe that the E-CADH-KRT7 combination is a very promising signature to predict HGSC patient prognosis and standard treatment response and could prove important when selecting the best treatment options.”
Interestingly, several studies from other groups have demonstrated that Keratin 7 has a strong prognostic value in other cancers such as gastric and pancreatic adenocarcinoma.
Finding ways to make ovarian cancer cells more sensitive to chemotherapy
A joint team of researchers in Quebec and Ontario has used samples from COEUR to make another important finding that has the potential to improve care for patients with HGSC. Published in the Journal of Clinical Investigation (April 2021), the finding identified a new target – a peptide called the relaxin receptor (RXFP1) – that when targeted, can make ovarian cancer cells more vulnerable to a commonly used type of chemotherapy known as cisplatin.
“Using samples from COEUR, we were able to show that the relaxin/RXFP1 signaling pathway plays an important role in the initiation and progression of ovarian cancer,” says Dr. Robert Rottapel, a senior scientist at the Princess Margaret Cancer Centre in Toronto and the paper’s senior author. “But more importantly we found that this pathway is a therapeutic vulnerability in OC: inhibition of RXFP1 increased chemotherapy sensitivity of OC cell lines and abrogated in vivo tumour formation.”
While the research must still be advanced, this finding demonstrates that targeting the relaxin/RXFP1 pathway may have therapeutic potential for treating a subset of patients with ovarian cancer, particularly in combination with standard cisplatin therapy, and could potentially overcome chemoresistance of platinum-resistant tumours.
A Keratin 7 and E-Cadherin Signature Is Highly Predictive of Tubo-Ovarian High-Grade Serous Carcinoma Prognosis
Laudine Communal, Noemi Roy, Maxime Cahuzac, Kurosh Rahimi, Martin Köbel, Diane M. Provencher and Anne-Marie Mes-Masson
Inhibition of relaxin autocrine signaling confers therapeutic vulnerability in ovarian cancer
Helen E. Burston, Oliver A. Kent, Laudine Communal, Molly L. Udaskin, Ren X. Sun, Kevin R. Brown, Euihye Jung, Kyle E. Francis, Jose La Rose, Joshua Lowitz, Ronny Drapkin, Anne-Marie Mes-Masson, and Robert Rottapel
These studies were partly funded by the Terry Fox Translational Research Program Grant to the Canadian Ovarian Experimental Unified Resource (COEUR)