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28 Jan 2022

Research reveals approach to improve therapy for childhood cancer

Researchers at Garvan have identified a potential therapy that may improve how effectively chemotherapy targets neuroblastomas.

Alex Swarbrick

A study led by the Garvan Institute of Medical Research has revealed a potential approach to improve outcomes for neuroblastoma, a rare but often aggressive cancer that is usually diagnosed in children under five years of age.

The team identified three microRNAs, short molecules of genetic material that turn off genes, which sensitised neuroblastoma cells to chemotherapy while leaving normal cell types unharmed.

If successful in further preclinical studies and clinical trials, these microRNAs may help make chemotherapy more effective for neuroblastoma patients.

“High-dose chemotherapy is part of the standard treatment for high-risk neuroblastoma, but there is a narrow window between efficacy and toxicity to the patient. These microRNAs may help open that window up,” says Garvan Lab Head Associate Professor Alex Swarbrick, senior author of the research published in the journal Molecular Therapy.

Potential strategy to improve chemotherapy

Improved treatment options for neuroblastoma are urgently needed. One in two children with an aggressive form of the disease pass away, with survivors often affected by chronic side effects following therapy. 

“High-dose chemotherapy can have significant side effects, especially in children. Our research has focused on finding a way to more effectively target a tumour with chemotherapy but that doesn’t impact normal cell types, so that the dosage given to patients can be reduced.”

Unlike adult cancers that are driven by mutations accumulated over a lifetime, early childhood cancers are instead often driven by changes in the genetic programs that control development.

“MicroRNAs are key regulators of development – they target different locations across the genome to ‘tune’ genetic systems. We tested 1,200 microRNAs for their effect on neuroblastoma cells,” explains first author Dr Holly Holliday.

“We identified three microRNAs that were potent chemosensitisers, meaning they enhanced the effects of chemotherapy on neuroblastoma cells without being toxic to other cell types. These microRNAs targeted a number of genes that are essential to neuroblastoma survival, which we verified in mouse models. By looking at prior studies, we also found they were often absent in patients that had a particularly poor prognosis,” Dr Holliday says.

“Together, this leads us to believe that restoring the function of these microRNAs by administering them to patients may be a valuable therapeutic strategy for neuroblastoma,” adds Associate Professor Swarbrick.

The next steps in this research will be to move to comprehensive preclinical studies, followed by clinical trials.

“We hope that this feasibility study will ultimately help improve treatments – getting a better hit on the cancer while dialling back the toxicity to the patient,” he says.


This research was supported by The Kids’ Cancer Project, Children’s Cancer Institute, the National Health and Medical Research Council and the Cancer Institute New South Wales.

A/Prof Swarbrick is a Conjoint Associate Professor at St Vincent's Clinical School, Faculty of Medicine and Health, UNSW Sydney.