Getting better results with less harm is the new approach to ovarian cancer treatment, explains researcher Professor Brian Gabrielli.
Hair loss, nausea, vomiting, fatigue and headaches – these are just some of the side effects cancer patients fear when faced with the prospect of chemotherapy. But what if there were another way?
With recent funding granted by the Ovarian Cancer Research Foundation, our team is testing a new treatment for ovarian cancer that promises fewer side effects. It does this by relying on the body’s own immune system to fight the tumour, instead of having to endure the wrecking ball effects that traditional chemotherapy has on the rest of the body.
Although current immune therapies have had great success in the treatment of cancers such as melanoma, it is much less effective in treating ovarian cancer.
One-two punch
My team at Mater Research and the University of Queensland will test whether combining a low, sub-clinical dose of two drugs – not previously used together – can help the patient’s immune system recognise and kill the cancer cells with minimal side effects.
We are using an existing chemotherapy drug, hydroxyurea, combined with newer inhibitors of checkpoint kinase 1, which plays an important role in regulating the body’s response to DNA damage.
I liken the effects of this combination to a phenomenon you might see in any Australian shed when using the epoxy resin glue Araldite. The individual components are ineffective, but the combination comes together in just the right way – becoming a great adhesive.
Our combination already shows promising results in animal studies for ovarian cancer with it not only blocking tumour growth, but the immune system appears to be responding to the tumour. Our idea is to use this combination to kill the tumour, treating the acute effects of the disease, and at the same time enhance the immune response to the tumour, essentially vaccinating the patient against their own cancer and improving effectiveness to achieve remission and reducing the chance of relapse.
The OCRF grant of $500,486 will be dedicated to validating and extending our findings. It is focused on getting a more detailed understanding of the immune responses triggered by the treatment with the aim of identifying specific immune targets to enhance and extend this anti-tumour response.
If successful, we will see whether this combination, plus the specific form of immunotherapy identified in our studies promotes a strong immune response in patients with high-grade, serious ovarian cancer, and determine whether such a response could improve long-term survival.
Pushing frontiers
New treatments are vital to reduce ovarian cancer deaths. While most patients with high-grade, serous ovarian cancer respond to standard chemotherapy, most of them will fail within a couple of years due to the cancer becoming resistant to available treatments when they experience recurrence.
Some patients will benefit from PARP inhibitors, but even those benefits can be short-lived. This means that there’s a lot of ovarian cancer patients who don’t have a viable alternative. Unlike chemotherapy, this immune-modulating therapy would leave patients with their immune system intact and also reduce the side effects that are a consequence of normal tissue toxicities.
My own wife underwent chemotherapy, which gave me a front row seat to its toxic side effects. This experience tells me we have do better. If nothing else, if it’s possible to simply remove the distress someone has to endure in order to just be treated — that would be a win.
I’ve seen women cut down in the prime of their lives after their ovarian cancer was sadly caught too late. So, working with groups like OCRF really does help researchers in the sector, particularly by meeting the people who are supporting us. It is a good reminder of why we do what we do.
It’s not an academic pursuit. It’s about changing outcomes for people.
ED: Professor Brian Gabrielli is a research fellow and head of the Smiling for Smiddy Cell Cycle Melanoma Research Group at Mater Research, and researcher at the University of Queensland.