Slowing prostate cancer progression

30 Nov 1999

With prostate cancer overtaking breast cancer as Australia’s most common cancer, the time has never been more critical to find treatment solutions for our nation’s men.

Dr Jenni Gunter and her colleagues at the Australian Prostate Cancer Research Centre of Queensland (APCRC-Q), may have some of the most promising answers yet, for the more than 24,000 Australian men a year who will receive a prostate cancer diagnosis.

Dr Gunter and the cancer metabolism group within the APCRC-Q are currently investigating two concepts, both of which relate to how cancer cells metabolize (use energy). The team are confident both methods when combined with existing treatments can give men diagnosed with prostate cancer more time with those they love.

“What we understand about the current therapies is that prostate cancer relies on one molecular feature to grow and that feature is the androgen receptor, the cancer can become resistant to therapy and then find ways to reinstate its activity,” Dr Gunter said. 

“With metastatic (advanced) disease, all the treatments are targeted on that androgen receptor in one way or another but we are beginning to see men who have survived on treatment for a long time emerging with disease that is no longer dependent on that androgen receptor, and we don’t have a way to measure or treat that.”

The team is currently investigating a unique enzyme pathway used by tumours to grow once they become resistant to androgen receptor targeting hormone treatments.

“I like to compare cancer metabolism with the map of the London underground and when we treat the tumour with something that blocks the access to Oxford Circus then the tumour is going to really quickly work out a new course to get to its destination,” Dr Gunter said.

“We looked at the data to examine how the metabolism is changing, because nothing can really happen unless the tumour is triaging its energy, pulling in the fuel it needs and organising where it needs to go, and we’ve identified a pathway that is routinely and predictably coming up that tumours are using to continue to grow. 

The way we analyse this sort of data relies on identifying pathway signatures that signal coordinated changes inside the tumour. The pathway we identified is oversimplified by this analysis and if we dive down into the data further, it's actually 3 parallel but independent lines which we're calling, identifying and treating as one.

“We have noticed that the tumour switches lines in this pathway. It goes from being dependent on one fuel to being really dependent on another type of fuel. 

“The useful thing about this switch is the more we treat things within the cancer the more they go back to more primitive metabolic pathways to try and grow which is kind of like the cancer putting its head on the chopping block. They become different to the behavior of normal cells which is fantastic because it gives us an in. For us that’s what this pathway represents. 

“The work we’re preparing to publish soon shows how we’ve been able to knock down a key gene (of this pathway) and affect cancer cells, but not normal cells and we know no one is looking closely at this.”

While the enzyme pathway research offers much promise, the APCRC-Q’s work repurposing drugs used to treat other conditions was made possible thanks to the PA Research Foundation’s donors and supporters.

The team discovered a diabetes medicine when used alongside existing treatments could be a new cancer inhibitor and potentially help slow cancer growth. Further studies also fund a decades old anti-malarial tablet had the same capabilities. Dr Gunter said the dilemma they now face though, which would halt this work in its tracks is ongoing funding.

“Our collaboration trial with PARF showed that if you gave men the drug metformin, you could reverse their metabolic syndrome that develops as a result of their androgen deprivation therapy and hormone treatment,” she said.

“We began to look at its effect inside the tumour as well and we compared it across other members of that biguanide (chemical compound) family. That’s where we found that there was an anti-malarial that’s been used for decades that we could potentially use as well.

“Even though repurposed drugs can be moved into the clinic really quickly, in terms of figuring out in which context we would use them and what combinations we would need, finding funding for that is quite challenging because there is not dollar signs at the end of that, there is patient outcomes.”

With research funding crucial to progress, Dr Gunter said the team is incredibly thankful for the support they’ve received so far. 

“I have such a belief in where this research can go, and I have days where I am completely motivated to keep pushing forward, and I have days when I get a grant rejection and I’m heartbroken because that’s the make or break to something that could make such a difference to patient survival,” she said.

“We take every single donation and grant that we get incredibly seriously because it is a tough landscape out there now and we have to make every dollar count. 

“I’m blown away by the generosity of people who can give even just $10 on PA Giving Day or the amazing people who are generous enough to think of medical research when they give larger donations.

“PARF funding has been fundamental to keeping our team together and watching our research emerge.”