Our ovarian cancer research
Ovarian cancer (OC) is the fifth most common cause of cancer deaths in Western women, but despite extensive research efforts survival has little improved over the last 20 years. OC is still largely treated as a single disease with surgery to remove as much of the tumour as possible, followed by six cycles of platinum-based chemotherapy. An early detection test remains elusive, evidence shows that screening is unlikely to be effective, and there are very few practical ways to reduce risk, apart from the use of the oral contraceptive pill.
By contrast, the discovery of the role of genetic mutations offers substantial opportunities for improving treatment for women with ovarian cancer, as well as reducing risk in their female relatives.
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Key areas of investigation
MoST clinical trials
The Genomic Cancer Medicine Program uses Garvan’s whole genome sequencing facilities in the MoST Clinical Trials to identify more effective treatments for cancer patients, as well as to understand heritable cancer risk in the Genetic Cancer Risk Study (RisC) and risk management as part of the Surveillance in the Multi-Organ Cancer prone syndromes (SMOC+) Study.
MoST patients are genomically screened to see if they're suitable and if there are variants that can guide the treatments. These trials are looking to see if a treatment will work, or work more effectively than another treatment.
After screening, patients are offered either:
- MoST clinical trials, including immunotherapies
- Clinical trials outside MoST that use molecular eligibility criteria
- Other biomarker-guided treatments outside MoST.
All participants, including those with no ‘actionable’ biomarkers are informed of the results of the screening through their own doctors.
MoST has already shown that genomic cancer profiling can identify treatable options for a significant portion of patients who previously had none.
Find out more about MoST Clinical Trials.
Long-term survivors and MOCOG
Only some 35–40% of HGSC patients survive five years, but a small number of patients – known as ‘exceptional responders’ – survive much longer to become long-term survivors (LTS). Led by researchers in the US, Canada, UK and Australia, the Multidisciplinary Ovarian Cancer Outcomes Group (MOCOG) was formed in 2013 to share data and identify women who would benefit from targeted immune therapy, as well as understanding genetic features associated with LTS that may lead to new treatments. MOCOG also looks at behavioural changes that may have had an impact on survival.
Some HGSC patients exhibit profound tumour shrinkage or complete clearance on initial chemotherapy with little or no recurrence, whereas others survive despite multiple cycles of recurrence and response to treatment.
Rapid responses to first line chemotherapy are likely to be driven by aspects of tumour biology that result in hypersensitivity to chemotherapy. In other women, effective immunological responses may result in relatively slow tumour growth.
While the extent of residual disease following surgery and chemotherapy is a significant predictor of outcome, approximately 45% of 10-year LTS actually have some residual disease, and approximately one-third have had recurrent disease. This strongly suggests that other factors, such as tumour biology and tumour immunity also contribute to LTS.
As in the women who respond well to platinum-based chemotherapy, in 75% of the HGSC patients who were still alive eight years after diagnosis, the HR DNA repair pathways of their cancer genes were inactivated, high-lighting the importance of HR pathway inactivation in survival in HGSC. It is possible that some LTS have more than one HR pathway mutation that could render tumours hypersensitive to chemotherapy, or reduce the likelihood of developing resistance.
It is now also recognised that lifestyle, environmental and genetic exposures influence the specific risks of OC subtypes in very different ways. We plan to contact living LTS to collect data on their lives pre diagnosis and what they did to help themselves after diagnosis, especially in terms of meditation, exercise, sleep, supplements, continuing to work and food and alcohol choices. Such behaviours may have helped the patient tolerate therapy such that she was able to receive full course, uninterrupted chemotherapy, or they may affect survival in other ways.
We believe it is important to look at the interactions between the immune, genetic and personal factors associated with LTS, and to specifically look at women who experienced an exceptional response (eg, women who had no recurrences during the 10+ year period), compared to women with more typical disease trajectories.