PA Research Foundation and its donors are bringing forward research into a potential game changer for the treatment of a disease that affects and sadly kills 1,405 Australians a year – melanoma.
The study led by Associate Professor Pascal Duijf aims to develop a new type of melanoma treatment, specifically targeting large genetic changes in the cancer DNA.
Many cancer patients are treated with what’s known as targeted therapies, drugs that target small genetic defects in the DNA of cancer cells. Where this study differs is it will target larger fractions of the genome in the hope of developing targeted therapies that can help thousands more patients whose melanoma has metastasized but is resistant to therapy.
Associate Professor Pascal Duijf with research collaborators Professor Nikolas Haas and Professor Andrew Barbour.
“Most targeted therapies target small genetic defects like mutations or small regions in the genome that might be lost or amplified. What they all have in common is that they target typically just one gene or sometimes several if it’s a deletion or amplification that includes two or three genes,” he said.
“What we’re doing differently is targeting deletions or amplifications of larger fractions of the genome, so more than one gene; it could be hundreds of genes even. The work we published in 2020 showed that if you try to predict how well cancer cells respond to drugs then these larger changes are far better predictors of how the cancer cells respond to drugs compared to the smaller deletions or mutations in the cancer cells’ genome.
“We thought it would be great to use this as a basis to see if we can actually develop therapies based on this, because it was just a prediction, and in order to really get from prediction all the way to ultimately treating patients you need to do multiple experiments to make sure that it is safe and actually works.”
The grant funding will be used to test the team’s hypothesis through examination in 2D and 3D cell systems in the ultimate hope that it will lead to a clinical trial and new hope for patients.
“We want to test if melanoma cells with these larger genomic defects do actually respond to specific drugs. What we want to do is look at it in a 2D setting such as a Petri dish and then in a more complex system,” A/Prof Duijf said.
“We will be collaborating with Professor Nikolas Haas who also works at the TRI (Translational Research Institute) and the University of Queensland Diamantina Institute. He has spent decades developing and optimising a three-dimensional culture system to culture melanoma spheroids. These are basically melanoma cells developed into spheroids or ball-like structures or spheres and are more complex.”
With many of the mysteries around cancer and how to treat it still yet to be uncovered, the PA Hospital campus based team of researchers keep their focus on working towards their primary aim - saving lives.
Though the current project is early-stage research, A/Prof Duijf believes long-term the work could excitingly bring hope to more than just patients with therapy-resistant melanoma.
“My primary interest is to develop something that helps patients so if it works and it is safe, then that is of more interest to me as compared to why it works,” he said.
“It’s not always clear how effectively certain drugs work in treating cancer, and part of the reason why is because every melanoma is a different disease. If you compare two patients, their melanomas will not be the same because what cancer cells have is lots of genomic and genetic changes.
“That’s why it’s difficult to know whether a drug will work in one patient but not in another. What we are doing might help us understand this and therefore helps us specifically treat these patients that do have these genetic abnormalities.
“In this project we’re looking at melanomas with four larger genetic gains or amplifications, our prediction is they sensitise the melanoma cells to drugs and we want to test this. If successful, then there are potentially other large defects in melanoma cells that could be targeted with different drugs. Ultimately all the patients whose cells have these genetic defects could benefit if we can get to clinical trials.
“I have a lot of compassion for people who have been diagnosed with and have been treated for melanoma and I recognise that it can come with a long medical trajectory involving surgery and treatments and it can impact people not just physically but also mentally, as well as family and friends that support patients.
“I’m incredibly grateful to everybody who supports research into melanoma and other cancers for that reason.
“There’s a lot of great treatments out there for melanoma and other cancers but unfortunately, they are not always successful. I think ultimately if we want to develop better treatments then we need to do biomedical research and research I think is the best way to improve outcomes.
“It’s a long investment which is often very expensive so that’s why I’m incredibly grateful for the support of the Foundation’s donors and supporters and advocates who at every level support cancer research.”
You can support game changing melanoma research by donating here.