Ovarian cancer, of all gynecologic cancers, claims more lives largely because there is no screening test and over 70% of women are diagnosed at advanced stages.
Ovarian Cancer research presents an opportunity to change the metrics on the outcomes of this disease. Investment in ovarian cancer research lags well behind that of other cancers, many of which have a much lower 5-year mortality rate 2. As an example, breast cancer has a 5-year mortality rate of 12%, prostate cancer’s 5-year mortality rate is 7%, while ovarian cancer is at 55%.
In the year 2000 OVCARE was established as a research partnership between Vancouver General Hospital and BC Cancer5. The goal was to advance basic and clinical research that could immediately be translated to the front lines on the prevention, diagnosis and treatment of ovarian cancer. Today, this diverse, dynamic team, with a shared vision, is recognized as in the top 3 ovarian cancer research groups globally, measured in terms of research and clinical impact.
British Columbia’s Pioneering Track Record
The output from this group has changed worldwide healthcare guidelines and practice impacting the care and treatment of women with ovarian cancer.
These are just a few examples of the successes and there are currently studies in clinical trials that will continue to influence the prevention, diagnosis and treatment protocols to save lives of women at risk of or diagnosed with ovarian cancer.
British Columbia also has another unique resource, that of the OVCARE Tissue Bank which is housed within the Vancouver General Hospital Department of Pathology and BC Cancer. This bank contains 56,000 tumour samples from over 6,100 patients5. The tissue samples in the bank are collected from consenting patients following surgical excision and stored in a variety of forms, enabling the extraction of genetic material for analysis. These tissues are used for cell culture, DNA sequencing, RNA sequencing, proteomics, patient derived xenografts (tissue graft) and imaging4. In addition to providing research material for OVCARE researchers, the OVCARE Tumour Bank is shared with national and international research collaborators and has already contributed to over 60 national and international research projects. Over the past two years, OVCARE has invested in reshaping this core research platform by integrating the tissue bank dataset with that of the clinical outcomes unit and linking them to all available research datasets (e.g. molecular, imaging, and pathology). This has created a comprehensive and valuable resource for gynecologic cancer research and leverages the significant wealth of data we have captured over the years fueling future research opportunities.
OVCARE continues to advance ovarian cancer research currently with the advanced technology of artificial intelligence, precision medicine, biologically driven therapeutics, and drug and immunotherapies.
OVCARE’S research includes world leading efforts to develop and test biologically informed prevention strategies and novel diagnostic and treatment approaches. We are building capacity in and developing a program that will address the biologic, social and cultural needs of survivors and their families. All research undertaken by OVCARE is shaped by knowledge gaps, patient need and the unique competitive advantages our provincially funded health care system and single medical school provide.
I. Biologically Informed Prevention Strategies
A. From Populations to DNA
Using BC as a living laboratory, we are determining how prevention strategies developed by our team (e.g. opportunistic salpingectomy – removal of the fallopian tube at the time of hysterectomy or in lieu of tubal ligation for permanent contraception) or known factors that influence risk (e.g. oral contraceptive pills) work to improve the impact of these opportunities to prevent cancer. This is achieved through our unique capacity to connect BC health care administrative datasets with our molecular pathology and genomic expertise. Through these studies we will determine the impact of opportunistic salpingectomy on the incidence of ovarian cancer in BC and other provinces in Canada. As an added benefit, we will also learn more about the cancers that are not prevented by this program. Further study will help determine the impact of the exposure to common medicines such as oral contraceptive pills or ACE inhibitors (commonly prescribed to treat high blood pressure) impact the development of ovarian cancers and shape their behavior.
B. From Precursors to Prevention
Through the direct genomic analysis of precursor lesions (cells that give rise to cancer) for ovarian and uterine cancers we are understanding how endometriosis sometimes transforms into ovarian cancers. Endometriosis, a common condition affecting 10% of reproductive aged women, occurs when epithelial cells in the lining of the uterus grow outside of the uterus such as on the ovaries. While endometriosis is considered a benign condition, some women with a history of endometriosis are at an increased risk of developing clear cell and endometrioid ovarian cancers, the 2nd and 3rd most common types of ovarian cancer. Our studies will shed light on potential markers that may predict a woman’s risk of developing endometriosis-associated ovarian cancers and map out the relationship between ovarian cancers and cancers that occur in the uterus.
II. Biologically Informed Diagnostics and Treatment Strategies
A. Discovery Genomics and Proteomics
Our team is continuing to lead efforts to determine the molecular features of several poorly understood ovarian cancers. Through a collaboration with Memorial Sloan Kettering Cancer Centre, we are mapping out how the most common ovarian cancer – high grade serous ovarian cancer – is shaped by the immune system to improve immunotherapeutic approaches. For these studies, we are using state-of-the-art single cell sequencing and proteomic approaches. Our research team has also recently completed the largest study on the proteome of clear cell ovarian cancer, the features discovered will be tested as diagnostics and developed as therapeutic targets.
B. Population Based Testing for Clinical Relevance
Once a potential diagnostic feature is discovered through our genomic or proteomic research, we will validate these results using large collections of ovarian cancer cases that we have built as a research resource through our leadership of national (TFRI COEUR) and international (OTTA; Ovarian Tumor Tissue Analysis) consortia. These resources enable us to produce definitive studies on biomarkers to determine their clinical value as prognosticators or diagnostics. This work will take place in our recently rebuilt molecular pathology research centre (GPEC; Genetic Pathology Evaluation Centre) at the VGH.
C. Model Systems
Having made the discovery of key mutations in several types of gynecologic cancer and used this information to improve diagnostics, our next major task is to determine how these discoveries can improve treatment. Through our tissue bank, we have established cell line models of different ovarian cancer histotypes (tissue types that arise during the growth of a tumour) which can be used for the study of subtype specific treatment approaches for ovarian cancer. OVCARE is also leading the development of mouse models for rare ovarian cancers which will be shared with the global community for drug development research. For common ovarian and uterine cancers, we have developed a novel approach to study the cancers “from the ground up” using organoids (normal cells from uterus, fallopian tube and ovary grown in a specific fashion to approximate the tissue these cancers arise from). This research will enable us to tease out how the specific cells of origins for these cancers along with the mutations that drive them and the tissue environment in which the cancers occur shape the development of the cancers and their response to known and novel treatments. This model system will also be used to better understand the key steps in the development of ovarian and uterine cancers and then to develop and test prevention strategies.
D. Preclinical Research
Using the research models developed as described in section II.C, we will test the response rates of cancer types to novel or repurposed drugs. This work will be performed in vitro (cell lines and organoids) and when leads are promising in vivo (mouse models).
E. Clinical Trials
Ultimately, treatment approaches need to be tested in rigorous clinical studies before they can be implemented as standard of care in the clinic. OVCARE is working to bolster its clinical trials capacity through strategic recruitment, investment in clinical trials infrastructure and pilot project funding. This effort is being developed in concert with the $10M federal funding committed for clinical trials in ovarian cancer nationally.