At the Research Awards 2024, we had the pleasure of hearing from Professor Anna DeFazio AM, University of Sydney, who heads the gynaecological oncology research laboratory at the Centre for Cancer Research, the Westmead Institute for Medical Research.
She is also the co-lead for the ovarian cancer stream at the Daffodil Centre*. The focus of Professor Anna DeFazio's research is to understand the clinical and genetic factors that influence response and resistance to chemotherapy in ovarian cancer.
In 2015, she established a major new study called INOVATe to optimise matching patients with new molecular targeted drugs and clinical trials. In 2020, Cancer Council NSW provided $3.7 million in additional funding for the second phase of this project, INOVATe 2.0.
Here's Adam Spencer's chat with Professor DeFazio AM.
Your work on ovarian cancer is so important. How long have we known about ovarian cancer as a disease?
Well, our work extends back to the mid-1990s. So, we've been working on ovarian cancer for a very long time. Interestingly, one of the things we found recently is that a lot of ovarian cancer doesn't even originate from the ovary. Even though we tend to call it ovarian cancer, much of it actually comes from the fimbrial end of the fallopian tube.
Is there essentially one type of ovarian cancer, or are there multiple types?
That's one of the complex things about ovarian cancer. Just by looking through a microscope, pathologists can see different types, like how some people in this room have blonde hair and others have dark hair. We've known that visually they look different and have been given different names. But with more research, we've learned that the molecular drivers - the genes that are mutated within these subtypes - are entirely different. Some are driven by oncogenes, others by tumour suppressor genes. The more deeply we study ovarian cancer, the clearer it has become that no two cancers are exactly the same. We can group them, but they are fundamentally different.
No cancer is pleasant, but is ovarian cancer particularly lethal?
Yes, ovarian cancer is particularly nasty. It has one of the highest mortality-to-incidence ratios of any cancer type. It's not very common, but many people die from it once diagnosed. The five-year survival rate is creeping up, but it's still under 50%. So yes, it's a very serious form of cancer.
What about chemotherapy? Is it still the main treatment for ovarian cancer?
Yes, chemotherapy is still the main treatment, but surgery also plays a critical role. Specialist surgeons - gynaecological oncologists - aim to remove as much of the cancer as possible. It's a very complicated surgery because the cancer can spread throughout the peritoneal cavity before there are any symptoms. The combination of surgery and chemotherapy has been the standard treatment.
Ovarian cancer sounds similar to pancreatic cancer in that, by the time symptoms appear, it might already be too late to treat effectively.
Exactly. By the time symptoms appear, cancer cells may have spread throughout the peritoneal cavity. When chemotherapy works, it works well at first, but unfortunately, the cancer often returns. That's when we need to explore other treatments. We've looked at what we call "extreme responders," where patients with widespread cancer have had remarkable, unexpected remissions. It's often a combination of the immune system and the changes in the cancer that lead to such outstanding responses. While these cases are rare, they give us hope that it is possible to achieve significant responses in more patients.
Tell us about the INOVATe study from 2015 and then INOVATe 2.0. What was INOVATe about?
INOVATe came after a decade of research that showed that ovarian cancer in one patient is not quite the same as in another. We did retrospective studies, looking at patients who had been recruited through the Australian Ovarian Cancer Study. We examined their samples, conducted molecular testing, and correlated that with outcomes. Around the same time, new drugs were being developed to target specific molecular alterations in cancers like melanoma. Some of these alterations also appeared in ovarian cancer.
The problem was, how do we use this information to change treatment? INOVATe was our contribution to ending the one-size-fits-all approach. Instead of working retrospectively, we started molecular testing at diagnosis to help patients immediately, not five years down the line. We then used this information to match patients with clinical trials and molecularly targeted drugs that were relevant to their specific cancer subtypes.
And how do these clinical trials work?
It's about recruiting only the patients with the specific marker for the drug being tested. If you gave the drug to everyone, but only 5% had the marker, the trial would appear negative. But targeting the right patients is complex because you may need to screen 100 patients to find just five with the marker. That's why we started molecular profiling at diagnosis, so we would know in advance which patients might benefit from a particular trial when they needed it.
What does "comprehensive molecular profiling" mean in this context?
It means testing for mutations that have known treatments or clinical trials available. We also did a test called HRD (Homologous Recombination DNA repair Deficiency), which identifies patients eligible for a drug called PARP inhibitors. That test is now available for all patients, funded by Medicare as of this year, which is fantastic. So, it's not just mutation testing; we look for changes we can act on.
You've worked closely with community and consumer groups. Why is that important to you?
It's crucial. We've always engaged closely with patients and consumers. They keep us honest. I meet with a patient support group at least once a year, where I explain what we've achieved. Their input gives us courage and direction. In fact, a consumer was the reason we re-applied for the INOVATe grant after it was rejected the first time. Without her encouragement, we might not have tried again.
The phrase "Discovering the next cancer research breakthrough takes all of us" was mentioned tonight. What does that mean to you?
It really does take all of us. Every single person - patients, their doctors, fundraisers, lab support staff, researchers - plays a role in moving this research forward. If everyone doesn't do their part, progress doesn't happen. It's truly a team effort.
