New therapies turning off energy for prostate cancer cells 

QUT-Australian Prostate Cancer Research Centre Queensland (APCRC-Q) researchers based at TRI are developing new drugs to shut down the energy pathways essential to prostate cancer cells’ survival.

Led by Dr Jenni Gunter, the Cancer Metabolism Group has identified potential treatment strategies, including a drug once used to treat malaria, which could be used to treat men with incurable, advanced prostate cancer. 

According to Dr Gunter, prostate cancer is responsible for the deaths of 375,000 Australian men each year.

“My colleagues and I have been searching for causes of treatment failure in advanced prostate cancer,” she said. 

“We’ve discovered that there are profound changes to the way tumours generate and use energy that allows them to become resistant to treatments.

“If we think of tumour metabolism as a river, therapies are used to build a dam wall. Tumours are able to get around the ‘wall’ or each new therapy, by re-coursing their cellular metabolism. If we can understand the precise route they take, we can target this new course and starve the tumour.

“Using cutting-edge technologies at TRI, we found cells switch to a pathway most used by fat cells or ‘adipocytes’ for energy and lipid production – both important pathways in prostate cancer. Blocking this pathway has profound effects on this energy re-coursing and cell survival, limiting their ability to manoeuvre around therapies.”

The research team also looked to see if they could repurpose drugs used to treat Type 2 diabetes.

In a pilot clinical trial in collaboration with clinicians at the Princess Alexandra Hospital, the team found one of these drugs, Metformin, led to an improvement in the metabolism of men with advanced prostate cancer.

“We aren’t the only ones who have looked at this drug to see if it can be used to improve the outcomes of men with prostate cancer, but this result was new, and it wasn’t something we were expecting at all,” said Dr Gunter.

The team has gone on to identify another drug belonging to the same family as Metformin, which in laboratory studies had an even more potent impact. A lack of funding, however, has meant that Dr Gunter has been unable to trial the drug in prostate cancer patients.

“This drug targets a pathway that no-one has yet looked at for prostate cancer, and we’ve been able to show its one of the key pathways the cancer is relying on while it reorganises itself,” she says.

“We believe this drug could be repurposed to improve patient survival, but unfortunately there isn’t a lot of commercial potential, so we’ve not been able to secure the funding to take this research any further.”

Dr Gunter’s group continues to map the metabolic pathways used by cancer cells, particularly the ‘primitive’ or basic ones they fall back on when key pathways are blocked by treatments.

“It’s well known that there is relationship between metabolic dysfunction and rates of cancer.

“Cancer cells are generally running at maximum capacity, and if put under stress, they can very quickly rewire and work out another route to get energy.

“We want to know what the typical re-routing that the cell will do in response to that primary therapy and are there existing targets to that or can we find other targets.”

Dr Gunter’s work has the potential to benefit patients across a range of cancers.

About Dr Jennifer Gunter 

Dr Gunter is a mid-career researcher, with a metabolic research background spanning more than 15 years. She leads a research team examining the metabolic plasticity of cancer cells with the aim of identifying therapeutic targeting strategies that extend patient survival.

Dr Gunter grew up in Albury, NSW and studied her undergraduate degree at the University of Technology Sydney (UTS).  After finishing her Masters, Dr Gunter took time off studying to travel, during which she completed her PhD at the Oxford Centre for Diabetes, Endocrinology and Metabolism at Oxford University. Her thesis examined lipid metabolism in islet cell biology related to type-2 diabetes and the emerging 'lipotoxicity' hypothesis.

In 2006, Dr Gunter returned to Australia with a University of Queensland Postdoctoral Fellowship at the UQ Diamantina Institute. In 2010, she joined QUT and the APCRC-Q at TRI to research the intersection between chronic metabolic disorders and their emerging relationship to cancer. These studies were focused on the role of insulin and the relationship between the insulin and androgen signalling axes.

Dr Jenni Gunter has authored 30 peer-reviewed manuscripts in high-impact journals, including eight first or senior-author papers, four reviews and three book chapters and has been awarded over $7.9 million in competitive grants.