Researchers seek to find a cure for the deadliest solid tumor in children

Australian researchers and oncologists have been awarded $2.4 million to investigate the causes and treatments for neuroblastoma, the deadliest and most common solid tumor in children under the age of five.

Associate Professor Yeesim Khew-Goodall and Associate Professor Quenten Schwarz from the University of South Australia and SA Pathology's Centre for Cancer Biology will lead two separate projects to identify the molecular drivers of neuroblastoma and find more effective drugs to fight it, using patient data in the first instance, and genetically engineered stem cells in the second.

The projects, involving the Women's and Children's Hospital and Royal Adelaide Hospital, are two of 106 groundbreaking medical research projects announced last week by the Federal Government under the Medical Research Future Fund, including $5.7 million for UniSA.

Neuroblastoma is a devastating disease which accounts for 15 per cent of all childhood cancer deaths, with fewer than 50 per cent of high-risk patients living five years after diagnosis.

"It typically affects very young children, mostly under the age of five years, with the average age of diagnosis around one to two years," says Assoc Prof Yeesim Khew-Goodall, a world expert in cancer and microRNA biology.

For high-risk neuroblastoma, relapse is not uncommon, and these children often need to undergo multiple rounds of therapy. Due to the young age of the children and the high toxicity of current treatments, which include chemotherapy and radiation therapy, those who survive can end up with debilitating side effects that stay with them for life."

Yeesim Khew-Goodall, Associate Professor, University of South Australia

Tumors form (typically in the abdominal region) when immature nerve cells called neuroblasts continue to divide and grow, developing into cancer cells instead of becoming functioning, mature nerve cells. Defective genes are thought to be partly responsible, but scientists are yet to find the definitive causes.

"Despite the highly toxic nature of current therapies, they are only effective in some children, so being able to predict which patients will or will not respond to current treatments will be our priority. Currently, there is a lack of reliable diagnostic criteria to predict disease course or treatment outcomes, and our aim is to fill that void."

Assoc Prof Khew-Goodall's $1.4 million project aims to improve risk classification using clinical information linked to molecular profiles of patient samples, and to identify therapeutic drugs that can be personalised for each child.

"We have found the first evidence that key microRNAs (molecules that regulate gene expression) are deleted in one type of neuroblastoma, for example. Increasing the expression of these microRNAs could be significant in stopping the progression of the cancer."

"At the moment, we have a sledgehammer approach towards treating neuroblastoma that can lead to developmental effects, including deafness, and problems with speech, mobility and cognition."

Assoc Prof Schwarz, a world expert in neuron development, will use genetically engineered stem cells to model the fetal origins of the disease and screen FDA-approved drugs.

"Stem cell modelling will help us mimic the disease process so that we can understand how different genetic alterations drive different forms of this cancer. We hope that this new information will allow us to identify the best therapies for each tumor type, as well as more accurately predict the patient outcomes," Assoc Prof Schwarz says.

"A major flaw of current treatment strategies is that they fail to treat the underlying cause of tumor growth. By modelling the disease, we will have better resources to identify new drugs for this disorder that are already approved for clinical use in other disease settings" he says.

The researchers will work with the families of current patients over the next three years, combining laboratory studies with patient profiling.