The latest research into genes and tumour mutations may offer new hope in the fight against one of the most tragic and challenging cancers – ovarian cancer.
Almost 1500 Australian women are diagnosed with ovarian cancer every year. At the moment there are limited options for prevention, and because of its unique characteristics it’s unlikely there’ll ever be a single, simple test to find it early. Ovarian cancer doesn’t have many symptoms, so it’s usually very widespread by the time it’s diagnosed. Then it’s hard to treat.
For researchers, it also brings up a key question – why has progress on ovarian cancer been so slow?
The survival rate for breast cancer is now more than 80 percent. For childhood leukaemia, almost 85 percent. Yet the survival rate for ovarian cancer has barely changed in 20 years, and currently stands at 43 percent.
Finally there is some good news, and Professor Anna deFazio, Sydney West Chair in Translational Cancer Research at the University of Sydney, is excited by what the current research suggests.
“Things are happening so quickly. We now have the tools to look at ovarian cancer very differently, and what we’re seeing could transform how we treat it.”
Working in translational research puts Professor deFazio at the interface between what happens on the research bench and how that translates to clinical practice, where patients become involved. She is part of a community of exceptional ovarian cancer researchers brought together by the University of Sydney and has also directed the Gynaecological Oncology Research Program at Westmead Hospital since 1995.
The key insights they are now working with have been provided by advances in molecular biology - one insight in particular has been profound.
“Being able to look at tumour mutations and genes on a molecular level has shown us that ovarian cancer isn’t just made up of the four variants that we can see by looking down the microscope,” Professor deFazio explained.
“Each of those variants has its own unique characteristics. It’s like every patient has their own brand of ovarian cancer. That’s one reason why the cancer is so elusive and why it’s so difficult to predict its response to treatment.”
These insights present new challenges, but they also lead to new, game-changing lines of thinking.
For example, the mutation of specific genes can make one woman’s cancer unique among ovarian cancers. This same gene mutation may also occur in another cancer. If a treatment already exists for this other cancer, would it also work for this matching type of ovarian cancer?
In at least one recent case, it seems the answer could be a resounding, yes.
A young woman, diagnosed in her 20s with a particularly resistant strain of ovarian cancer, had run out of treatment options. Primary treatment had failed and chemotherapy wasn’t working. The cancer had spread throughout her body and she was on morphine for the pain.
The patient’s medical oncologist, University of Sydney researcher and director of the Sydney West Translational Cancer Research Centre Professor Paul Harnett, could see just one more opportunity to save her. He knew the young woman’s ovarian cancer contained a mutation in a gene called BRAF – the same mutation that often occurs in melanoma.
A highly effective new melanoma drug that had first been trialled at Westmead was now on the market. It wasn’t indicated for use in ovarian cancer, but Professor Harnett approached the drug company for what’s called ‘compassionate access’. The company agreed and this young woman became one of the first people in the world to receive this treatment for ovarian cancer.
"Almost immediately, her blood tumour marker level began to fall and fall, till for the first time in seven years, it returned to normal,” Professor deFazio said.
“The tumour started to melt away. She’s now off pain killers and back at work.”
Professor deFazio will not call this result a cure for ovarian cancer. The young woman had a rare form of ovarian cancer and an even more rare gene mutation. In her very particular case, the melanoma drug therapy worked brilliantly. It may not work for others. It’s also far from certain what the medium to long-term outcome will be.
What this result does do is demonstrate a mechanism that Professor deFazio thinks has incredible promise.
She and many other University of Sydney researchers are pursuing this promise through a program called INOVATe - Individualised ovarian cancer treatment through integration of genomic pathology into multidisciplinary care.
Cancer research at the University is supported by the Cancer Research Network, established by bequests and donations to support all areas of cancer research. INOVATe itself has also benefitted by a $3.7 million grant from the Cancer Institute NSW.
As women are diagnosed with ovarian cancer, they will be invited to become part of the INOVATe study. Their tumour samples will be tested and the information added to the INOVATe information portal along with the 2000 women already recorded.
The portal is currently a research tool but the goal is to turn it into something clinicians can use, so they can instantly see how their patient fits into the broader ovarian cancer picture. At the top of the INOVATe wish list is to have a button on the portal that the doctor can click to be told the right drugs to give a patient with that particular ovarian cancer profile.
“We’re not even nearly there yet,” Professor DeFazio said, “but it’s incredible that we’re in a place where we can even contemplate something like that. It will be amazing.”
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