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Molecular feedback loop causing neuroblastoma has been discovered

 
ACRF
ACRF
November 5, 2015

Researchers at Children’s Cancer Institute have identified a molecular ‘feedback loop’ that accelerates the development of neuroblastoma, a cancer of the nervous system in children. Fortunately, the research team has also identified an experimental drug, currently in clinical trials for adult cancer, with the potential to interrupt the loop and halt tumour progression.

Researchers showed in laboratory models of neuroblastoma that the drug could block the very start of this embryonal cancer, paving the way to possible prevention strategies in the future.

They found that a combination of the drug – known as CBL01371 – used in combination with traditional DNA damaging chemotherapy agents was much more effective than either drug alone.

Professor Michelle Haber AM, leader of the Experimental Therapeutics laboratory and Professor Glenn Marshall AM, leader of the Molecular Carcinogenesis laboratory at Children’s Cancer Institute, worked on two very different aspects of the study.

Professor Marshall’s team focused on the genetic and molecular mechanisms behind the feedback loop, and its interruption by CBL0137. Professor Haber’s team focused on the therapeutic potential of CBL0137, both as a single agent and in combination with other drugs.

“Our laboratory tests tell us that CBL0137 is likely to be very effective against the most aggressive neuroblastomas, and indeed the most aggressive forms of other childhood cancers, and that is very exciting,” said Professor Haber.

“But what is particularly exciting is that, in contrast to many other chemotherapeutic agents, CBL0137 does not damage DNA, and it is DNA damage that is responsible for the many unpleasant and serious side-effects that frequently affect children after they are cured of their cancer.”

“The drug is currently in Phase 1 clinical trials for adults, which means that safe dosage levels are being tested. Once the adult trials are completed, a Phase 1 trial for children with refractory – or relapsed – neuroblastoma, and also other aggressive childhood cancers, will open in the United States and Australia,” Professor Haber said.

Neuroblastoma, the most common childhood cancer

Image: cross-section of neuroblastoma cells

Neuroblastoma is the most common solid tumour cancer of early childhood, and is generally diagnosed when the disease is advanced. Around half of all children with neuroblastoma have aggressive tumours, and fewer than half of these patients survive, even after intensive treatment.

These findings are published today in the journal Science Translational Medicine.

This  news item was originally published on the Children’s Cancer Institute’s website. The original version provides more detailed scientific information on the study.

ACRF has supported cancer research at the Children’s Cancer Institute by providing three major grants, totalling AUD 5.1m.

All images courtesy of Children’s Cancer Institute. Feature image, clockwise from left to right: Professor Glenn Marshall, Dr Dan Carter, Professor Murray Norris, Professor Michelle Haber, Jayne Murray

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