Researcher Highlights
Finding answers to cancer’s complex problems

Dr Moira Graves always hoped to forge a career in research, and now she’s found a home in a team who like ‘poking a problem’ as much as she does.

Moira started her career in pathology, but there was always a part of her that was drawn to research. After spending a number of years working around Australia, Moira moved to Newcastle and found her research niche.

“Once my boys were in school, I thought about what I really, really wanted to do, and I realised that I’d always wanted to do research.” After completing a Masters at the University of Sydney, Moira had the chance to work with Laureate Professor Rodney Scott in his genetics lab. This led to a PhD in Multiple Sclerosis, and where Moira immersed herself in the complexities of genetics research.

However, it was family that really helped her decide her research path. “Toward the end of my PhD candidature my brother called me and told me he had a recurrent pain in his upper leg, he said it felt like a big orange – so I told him he had to go straight to a Doctor and get an MRI,” Moira says.

“He was diagnosed with stage four metastatic melanoma. The orange-sized lump was a cancer tumour, and it had spread to his lymph nodes, his liver and his lungs. They basically sent him home and gave him six months to live.”

However, upon seeking the advice of her work mates, Moira found out about an innovative clinical trial in melanoma. “So I got on the phone and told him to catch a plane from Townsville to Sydney,” Moira adds. “He ended up being one of the first people to go on this clinical trial with two new drugs which were BRAF/Mekinhibitors. Within a few months the cancer had shrunk down to the size of a golf ball, and in 12 months it was gone. He was one of the first people in Australia who had more than five years response to that treatment.”

This experience set Moira on a determined path. “Because of where he lived, he was basically told to go home and die. If you didn’t live in Sydney or Melbourne, you didn’t have the option to enroll in a clinical trial and have the best chance to live.”

Moira joined Associate Professor Nikola Bowden’s team at HMRI and they started working on treatment-resistant melanoma. Since 2015, they’ve developed two trials for people who initially respond to treatment, but then develop a resistance and relapse.

“We’re working on a way to re-prime their immune system so they can go back on a drug that was working to fight the cancer,” Moira says.

Cancer is a complex beast, and melanoma is particularly challenging. “When I first started working with Nikola, we tried to work out how melanoma cells are so good at evading the immune system. They’re experts at it. We needed to find a way to make those tumour cells have little lights on the outside that say, ‘here I am, come and get me’.”

Working with two off-patent drugs (which are readily available, and cheap to buy) the team uncovered that these drugs could encourage the DNA to create an abnormal protein that served as a little light that made the cells identifiable as abnormal.

“Once the immune system recognises something as abnormal, it attacks it, but cancer cells are skilled as disguising themselves and blending in with the body,” Moira says. “Melanoma is basically the body’s response to damage, and the DNA mutates because of UV damage. So we’re working with the body to get the immune system to work to repair DNA – and take out the tumour’s advantage so the body can repair naturally.”

Switching focus to the brain

Moira is now transferring her knowledge to another complex cancer, glioblastoma – one of the most deadly forms of brain cancer. “Working with the team, we’ve partnered with Merck on Melanoma, and because we’re working on DNA repair, they thought we could trial these drugs on glioblastoma,” Moira explains.

The drugs were developed to treat another form of cancer, but after many stages of trials the company discovered that these drugs were no more effective at treating the cancer than existing treatments. So Moira and the team sat down, looked at what the drugs were doing in the body and looked to repurpose them for brain cancer and ovarian cancer.

“These two cancers have very few, if any, effective treatments once they relapsed past a certain treatment,” Moira explains. “I put in for an HMRI grant, which we were awarded, and we started working with these drugs and brain cancer cell lines. We got some promising new data that showed that combining these new drugs with the old treatment actually increased the cell death in these tumour cells.”

“We applied to the Mark Hughes Foundation and was awarded a grant of $200 000 and a PhD student named Mat is working on it. He has shown that after the brain cancer patient relapses and the tumour comes back, the tumour is  not as sensitive to the drug they were first using. So what we’re doing is seeing whether combining a new DNA inhibitor with this existing drug makes the treatment more effective.”

“We’ve been working with the radiation team down at Lake Macquarie Private and we think we have found a new job for one of the four Merck drugs were trialing,” Moira says. “When combining the new drug with the old drug after radiation, the tumour cells started to die more effectively. These new drugs have already gone through phase 1 trials, so we know about the expected side effects, so the time to a clinical trial is much shorter. Hopefully a clinical trial for brain cancer could start in 2021.”

One of the things that Moira enjoys most about her job is problem solving, and she’s found herself in the ideal team to do so. “You’ve got to find people who are not the same as you, and who’ll come at a problem from a different angle,” Moira says. “We’ll throw ideas around, poke them and prod them, and then we’ll go into the lab and see if it’s going to work. I like being challenged.”

The work Moira’s doing comes at cancer from a different angle. “I don’t think you can ever eradicate cancer, because cancer is actually a part of you,” Moira explains. “If you try to kill every single tumour cell with aggressive treatment, your quality of life will be poor. What we want to do, is help people live a good quality life, go back to work, and live with their cancer so it’s more like a chronic disease than a death sentence.”

“We won’t eradicate it, but we will contain it so you can live the life you have chosen to lead.”