The DNA of Ovarian Cancer Research
An estimated 3,000 Canadians will be diagnosed with ovarian cancer in 2022. An estimated 1,950 will die from it.1 The signs and symptoms of ovarian cancer are vague and often the cancer progresses to a late stage before it’s diagnosed. It’s a devastating disease that impacts people at the start of their careers and often at a time where they have young families and elderly parents.
Although overall survival rates haven’t improved much for patients with ovarian cancer over the last decade, much has been learned about the disease itself. Better genetics and histologic analysis have revealed the origin and subtypes of the disease; immunologic studies have demonstrated where there might be weaknesses in the tumours that might be exploited for therapy, and patients themselves have been empowered through lifestyle changes to impact the course of their disease. Researchers are asking whether current treatments are the best ones, and designing clinical trials aimed at improving outcomes and lowering toxicities. With better drugs and more precise treatments, patients may be able to undergo less aggressive regimens and enjoy a better quality of life.
Across Canada, researchers interested in ovarian cancer are collaborating to beat ovarian cancer. Sharing model systems and expertise, findings, and working together to go farther. Patients with or impacted by ovarian cancer are now being included in research projects, and not just as study subjects but in the evaluation, design, and execution of research, providing new insights into the disease and where priorities should be. From lifestyle to cells, attacking ovarian cancer from multiple angles are BHCRI members Melanie Keats and Jeanette Boudreau
The role of BRCA genes is to encode DNA repair enzymes. When one or both fail, cells cannot repair mutations, making them more likely to become cancerous. BRCA1 and 2 are major members of a family of DNA repair enzymes, and cells can function without some, but not all of them. One of the biggest improvements in ovarian cancer therapy in recent years has been the introduction of PARP inhibitors like olaparib, niraparib, rucaparib and talazoparib. These drugs inhibit enzymes meant to repair DNA damage; paradoxically, in a cell that already has mutations in some DNA repair enzymes, inhibiting more signals the cell to die. Of course, these work best in patients that have mutations in DNA repair enzymes, which is why studying the patients’ genes is so important.
Not every patient is a candidate for PARP inhibitors, and those drugs (along with surgery, and other chemotherapy) might only partially control the disease. Ovarian cancers mutate and metastasize often and can exist as both a solid tumour or as a fluid or liquid-like tumour (ascites) which makes targeting them even more challenging. An emerging treatment option for ovarian cancer is immunotherapy, which uses the body’s own immune system to attack and kill cancer cells by redirecting or reactivating the immune system to respond to and control tumours. The immune system is especially effective in cancers that carry a high number of mutations, because these mutations create targets. Presently, immunotherapy isn’t as effective in ovarian cancer as in other cancers, but combined with other chemotherapies and drugs, or designed to be agile and target many features at the same time, immunotherapy might be important for supporting tumor control or reducing toxicity from high-dose chemotherapy regimens.
One of the most significant risk factors for ovarian cancer is an inherited genetic mutation in one of two genes: breast cancer gene 1 (BRCA1) or breast cancer gene 2 (BRCA2). These genes are responsible for about 10 to 15 percent of all ovarian cancers.
Natural killer cells (NK cells) may be one answer. NK cells are specialists at recognizing cells that are damaged and exhibit signs of stress, but they recognize hallmark features of stress and damage, not specific antigens. BHCRI member, Dr. Jeanette Boudreau has been studying samples collected from patients with ovarian cancer, to try to understand how the tumour interacts with NK cells and what the features of good and bad responses are. “We are interested in understanding what makes an NK cell a good collaborator in controlling the disease”, says Dr. Boudreau, an Associate Professor in the Department of Microbiology and Immunology at Dalhousie University and Dalhousie Medical Research Foundation Cameron Cancer Scientist. “We have found that a subset of NK cells is associated with better outcomes and better immune cell interactions within the tumours. Now we are building model systems to figure out why this happens and what encourages these specific NK cell subsets to enter tumours. If we can control the immune system and how it engages with tumours, we will be able to help more patients with ovarian cancer to live longer and more enjoyable lives.”
Treatments are improving, but for many patients, ovarian cancer never completely goes away. These patients will undergo continuous monitoring and may experience relapses, requiring additional treatments. Learning to live with this disease can be very stressful.
This is where physical activity can help. Physical activity/exercise can empower patients to become active participants in their health care and can assist them in managing, coping with and recovering from both the disease and side-effects from toxic treatments. Interestingly, exercise has been shown to increase NK cell activity and while much is left to be explored, exercise may play an important role in overall survival.
Enter Dr. Melanie Keats, BHCRI member and Professor in Dalhousie’s School of Health and Human Performance. Dr. Keats’ research is dedicated to the study of physical activity/exercise and cancer survivorship. “My research interests include the examination of the impact of physical activity/exercise on cancer related health outcomes and quality of life; investigating the prevalence, determinants and activity preferences of cancer survivors and exploring the effectiveness of interventions designed to promote physical activity across the cancer continuum.”
Ovarian cancer research is underfunded. We asked the researchers featured in this story: what would you say to someone reading this article about why they should consider giving?
“Ovarian cancer remains a very challenging disease to diagnosis and treat. With over 30 different types of ovarian cancer, there is a need to better understand the disease to improve early detection efforts and so that treatments can be better targeted to manage, what for many patients is a non-curative disease. Compared to other cancers, ovarian cancer research is substantially underfunded. As a 4-time cancer survivor, I am grateful for all those who support and conduct cancer research. As an ovarian cancer survivor, I have become acutely aware that ovarian cancer deserves more.” – Dr. Melanie Keats
“Outcomes for ovarian cancer haven’t improved as quickly for ovarian cancer as they have for other cancers, and the disease impacts young people and families. The cancer itself – especially the rarer subtypes – is poorly understood, and more research is needed to figure out the best ways to treat it. The research that has been done so far is giving better and better insight, and its coming at a time when hospitals are better equipped to deliver more precise care. Donating to support ovarian cancer research will support multidisciplinary teams of researchers, physicians, and patients to help beat a devastating disease.” – Dr. Jeanette Boudreau
We are all hoping that we will continue to see improvements in disease detection leading to earlier diagnosis, identification of genes that put some at a higher risk of ovarian cancer, an improved understanding of how the disease works, and advances in our knowledge of how to best treat this disease.
For more information on ovarian cancer, visit Ovarian Cancer Canada