Therapeutic cancer breakthroughs and predicting cancer spread

Therapeutic cancer breakthroughs and predicting cancer spread

La Trobe Senior Research Fellow, Dr Belinda Parker, is an expert in breast and prostate cancer research.

She was recently awarded an NHMRC Project Grant to predict likelihood of early stage breast cancer relapse; a Prostate Cancer Foundation Australia Program Grant to find new therapies to block bone metastasis in prostate cancer; and Cancer Council Victoria funding to develop immune markers that predict aggressive forms of breast cancer.

Last week, the Victorian Cancer Agency announced Dr Parker had received its four year mid-career research fellowship to identify ways to individualise therapy for patients with triple negative breast cancer.

Dr Parker discusses the complexities of the disease, therapeutic breakthroughs and her search for markers to predict cancer spread.

Stopping cancer spread

Dr Parker’s ‘bench to bedside’ approach has defined her research career. ‘I decided early on that I wasn’t going to stay in science unless I could do something that made a difference to health,’ she says.

Her PhD, undertaken at La Trobe University with Emeritus Professor Don Phillips, focused on improving chemotherapy treatments for breast cancer patients. It was her postdoc at Johns Hopkins University in the United States, however, that sparked her interest in cancer cell behaviour.

‘There, I began to look at the biology of cancer and what makes it more likely to spread,’ she said. ‘I was awarded fellowships to come back to Australia to determine what changes in a cancer cell to allow it to grow in the bone.’

Cancer spread can develop up to twenty years after a woman’s initial breast cancer diagnosis. ‘The cancer cells,’ explains Dr Parker, ‘eventually find a way to overcome the immune system.’

The same thing happens in prostate cancer, where cancer spread sometimes takes years to develop, and usually invades the bone. The similarities in the metastatic process led Dr Parker to expand her research focus.

‘We have found that the immune pathways critical to breast cancer spread are also important to prostate cancer. In both cases the cancer cells shut down particular immune signals that allow them to thrive in the bone. We are working to switch those immune responses back on to prevent bone spread.’

Cancer cells being confined to the duct by myoepithelial cells (courtesy Natasha Brockwell)

Dr Parker’s lab is also partnering with biopharmaceutical company, AstraZeneca: using their pre-clinical models of breast cancer, they will trial the company’s new immune activator to see if it has an impact on metastasis.

‘We can take what we know about the nature of the cancer cell and why the immune system is reacting in different ways to cancer, and link that to therapies that are immune based,’ she said. ‘If we get to human trials, we will take those tissues back from the clinic, and onto the bench again, so that we can determine who is getting the most benefit from these therapies.’

Predicting metastasis

Improving cancer treatments is one thing, but Dr Parker also specialises in determining who needs these therapies in the first place.

‘From mammogram screening, 25 percent of women will be diagnosed with “ductal carcinoma in situ”, where cancer is confined to the breast ducts and surrounded by healthy, myoepithelial cells that work to strengthen the duct lining,’ she explained.

‘Most patients receive radiotherapy, but never have an invasive relapse. So, essentially, they are receiving radiotherapy because we cannot predict who will end up with cancer spread.’

Parker and PhD student, Hendrika Duivenvoorden, are examining the interaction between myoepithelial cells and cancer cells in these very early breast cancer lesions to determine who is likely to go on to develop metastasis.

‘We have identified markers in the gatekeeper cells around the cancer cells that appear to predict whether invasion will occur,’ said Dr Parker.

‘We are now screening 500 patient samples from the Royal Melbourne Hospital, which is probably the best long-term patient cohort in the world that hasn’t received therapy.

‘We will be able to use these samples to determine if measuring this marker in the gatekeeper cells can predict the risk of cancer coming back at a later date.’

Parker Lab

Making an impact

So what is it like working on cancer discovery? ‘Being in a competitive research environment has its challenges,’ Dr Parker admits.

‘At times I feel like my lab is up against large groups of over 30 people that have unlimited resources and are producing data very quickly. But it doesn’t put me off at all. It drives me further.

‘My lab focuses on tumour immunology that is translational. We strive to do things in a way that is unique, and thorough, and are always mindful of how it will impact the clinic.’

‘I want to give people peace of mind. A woman may have breast cancer, but let’s work out if she is going to be okay for the next twenty years, if current therapies are going to be enough, or if she needs other intervention. Is she a candidate for immunotherapy?

‘That way, we are tailoring the therapy to people who could really benefit from it, while sparing others unnecessary treatment.’

So what’s next? ‘I think the biggest discovery in my lab will happen in the next couple of years,’ Dr Parker said. ‘With funding from the NHMRC and Cancer Council Victoria, my fellowship with the Victorian Cancer Agency and partnership with AstraZeneca, we are pulling all our work together, and testing whether we can find markers to predict who should be receiving therapies aimed at switching the immune system back on.

‘It could be the highlight of my career – if I can take what I know about a cell in the lab and use that to individualise therapy for a patient, well, that would be the greatest achievement of all.’

Find out more about how the La Trobe Institute of Molecular Science is solving global problems at the interface of health and science. 

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