Paediatric high-grade gliomas are aggressive brain and spinal cord tumours that are the leading cause of cancer-related death in children. Radiotherapy is the mainstay of treatment, but cure is very rare, and recent UK treatment guidelines therefore emphasise the urgent need for novel therapies to be tested alongside radiotherapy.
Prof Hammond’s previous studies have shown that combing Ag5, a small silver-based drug, with radiotherapy increases the damage done by radiotherapy to cancer cells. This project will explore whether combining Ag5 with radiotherapy can safely and effectively improve outcomes for children with paediatric high-grade gliomas.
Paediatric high-grade gliomas (pHGG) are aggressive brain and spinal cord tumours and are the leading cause of cancer-related death in children. Most children are diagnosed between the ages of 5 and 15, and survival is typically less than 15 months. Despite decades of research, outcomes have not significantly improved, and current treatments remain limited. Radiotherapy is the mainstay of treatment, but many children experience tumour regrowth, proving that some cancer cells survive radiotherapy. Chemotherapy offers little benefit and can cause significant side effects, especially in the developing brain.
Recent UK treatment guidelines emphasise the urgent need for novel therapies to be tested alongside radiotherapy. One potential target is the high level of reactive oxygen species (ROS) in paediatric high-grade gliomas. These unstable molecules are produced by cancer cells and make cancer cells more likely to have further increases in ROS. Ag5 is a small silver-based drug that becomes active only in environments that have high levels of ROS, such as paediatric high-grade gliomas, while sparing healthy brain tissue.
Prof Hammond’s laboratory studies have already shown that combining Ag5 with radiotherapy leads to greater cancer cell death than radiotherapy alone. This project will explore whether combining Ag5 with radiotherapy can safely and effectively improve outcomes specifically for children with paediatric high-grade gliomas.
In this project Prof Hammond and her team will test whether combining the silver-based drug Ag5 with radiotherapy can safely and effectively treat aggressive brain tumours in children.
First, the team will study how Ag5 works in cancer cells grown in the lab. The team already know that Ag5 targets tumours with high levels of unstable molecules called reactive oxygen species, which are common in these cancers. The team will therefore test whether Ag5 increases the amount of damage caused to the cancer cells by radiotherapy, and will explore what type of cell damage this combination causes — for example, whether the cancer cells die, stop growing, or become more vulnerable to other treatments.
Next, the team will test the combination in specially designed models of paediatric brain tumours, using tumour cells that closely match what is found in children. The team will monitor tumour growth and overall health using imaging techniques and assess how well the treatment works compared to radiotherapy alone. They will also check for any unwanted effects on healthy brain tissue to make sure the treatment is safe.
The overall aim of the project is to gather strong evidence to support future clinical trials using Ag5 alongside radiotherapy to improve treatment for children with these devastating cancers.
If successful, this project could lead to a completely new way to treat paediatric high-grade gliomas — one that targets the cancer’s own vulnerabilities while protecting the developing brain. This is especially promising because: Ag5 can be used with existing treatments like radiotherapy; it has the potential to improve survival in a cancer with very limited options; and the therapy could be ready for clinical trials relatively soon, especially since it aligns with current UK guidelines encouraging novel treatments in paediatric high-grade gliomas.
The project could also provide data that impacts future studies investigating the use of Ag5 for the treatment of adult disease.
Prof. Hammond is a radiobiologist with a long track record of research at the University of Oxford focused on improving radiotherapy response rates.
Dr Monica Olcina (University of Oxford) is an early career researcher who works closely with Prof Hammond, including as part of a large EU funded consortium focused on improving outcomes for paediatric high-grade gliomas.
Dr Anna Rose (University of Oxford) is a paediatric oncologist and runs a lab focused on certain types of cancers, including paediatric high-grade gliomas. Dr Rose will provide scientific insight and expertise into the role of the protein ATRX in response to Ag5, as well as knowledge of the clinical situation for affected children.
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