Targeted Treatment for Childhood Brain Cancers

Research funded by the Children’s Cancer Foundation over the past two years has greatly increased understanding of the genetic changes that cause childhood brain cancers.

The research team, led by Dr Dong Ahn Khuong Quang and Associate Professor Paul Ekert, from the Murdoch Children’s Research Institute is combining several genomic techniques to identify genetic changes that occur in brain cancers.

These techniques allow researchers to map the entire genome of a patient’s cancer in one go, identifying the genetic changes that are likely to be important in triggering cancer and investigating the factors that cause these changes.

The project focused on paediatric brain tumours, the second most common childhood cancer, as they haven’t benefitted from the same advances in treatment as other childhood cancers over the past 20 years.

“There are many different types of brain tumours and we need to characterise them the best we can so we can have a more personalised approach to each patient,” Dr Khuong Quang said, a trained oncologist and lead investigator of the project.

“Every tumour is a little bit different: they all have very specific and sometimes unique profiles,” she said.

Through detailed analysis of individual tumours, researchers can explore new and targeted treatments with the hope of treating and curing each patient individually.

“I am more and more convinced that – especially for the tumours that are highly aggressive – we have to understand that chemotherapy and radiation won’t be enough,” Dr Khuong-Quang said.

“There are some patients with brain tumours that we know how to treat and to cure, but when young children undergo radiation therapy it can affect their development and have long-term side effects.”

Currently, the techniques are being applied to individual cases from The Royal Children’s Hospital with unusual findings for the purposes of research.

Similar techniques to assess specific genomic changes are being applied to most children with brain cancers in Victoria through the AIM Brain project, which Dr Khuong Quang is also supporting through patient recruitment.

According to Dr Khuong Quang and A/Prof. Ekert, research like this ‘Targeted Treatment for Childhood Brain Cancers’ project and the Hudson Monash Paediatric Precision Medicine program, also funded by the Children’s Cancer Foundation, will be the impetus to make genomic analysis available to all children with cancer who can benefit.

From the advances in knowledge about specific tumours already made in the study, Dr Khuong Quang and A/Prof. Ekert have discovered changes in tumours that have allowed the clinicians to investigate targeted treatment.

The ultimate goal of genomic analysis is to provide feedback in real time to directly benefit the management of a child’s treatment plan.

Dr Khuong-Quang said when they identify an abnormality that they think is driving the cancer growth, they are able to take it back to the lab and test it against different drugs to try to identify which possible therapies may work.

“One of our patients was only one year old when he was diagnosed with a brain tumour that couldn’t be removed entirely through surgery,” she said.

“RNA sequencing found a very rare lesion, which opened the possibility of offering a targeted therapy. After our finding was validated, this patient was then enrolled on a clinical trial in Sydney and is now much better with improved scans. We feel that without this RNA sequencing he would be in palliative care or worse by now.

“So the more targeted treatment we can develop through RNA sequencing, the more we will minimise the side effects,” Dr Khuong Quang said.

Through the project, researchers also hope to develop a frontline blood test that can be used to screen the genetic nature and profile of a tumour before any major surgery or biopsy.

This simple test could potentially prevent young patients being exposed unnecessarily to treatments that may have lifelong consequences.

Dr Khuong-Quang in the lab