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Researchers Identify New Target for Treatment in Children's Cancer

Staff
December 22, 2008 (Added)
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Australian researchers have identified a potential new target for treatment of neuroblastoma, the mo...

Australian researchers have identified a potential new target for treatment of neuroblastoma, the most common solid tumour among young children, as published in prominent international cancer journal, Cancer Research.

Professor Michelle Haber AM, Executive Director, Children's Cancer Institute Australia for Medical Research (CCIA), said the findings were an exciting development towards one day finding an eventual cure for this childhood cancer.

Cancer researchers have long known that the presence of multiple copies of the cancer-associated gene, MYCN, in neuroblastoma tumours is a powerful predictor of death in this disease. It has also been known that MYCN drives the expression of many other genes including one in particular called ODC1.

"Patients whose tumours carry multiple copies of the MYCN gene, have a particularly poor prognosis and new therapies are urgently needed, said Professor Haber.

"Our findings indicate that over expression of the ODC1 gene contributes to the aggressive biology of this tumour and poor clinical outcomes.

Using a laboratory model of neuroblastoma, researchers tested whether inhibiting ODC1 activity with difluoromethylornithine (DFMO), a drug known to suppress ODC1 function, would improve treatment of neuroblastoma, when used in combination with conventional chemotherapeutic drugs.

"We found that the combined drug treatment prolonged tumour-free survival compared with chemotherapeutic drugs alone, suggesting that targeting ODC1 for suppression is a potentially valuable therapeutic approach," said Professor Haber.

"By inhibiting the action of the ODC1 gene, we also found that the development of neuroblastoma could be delayed or even prevented, again highlighting the importance of this gene in the aetiology of this disease.

The next step will be to test DFMO in combination with other chemotherapeutic agents, particularly newer agents that might be most effective in treating drug-resistant disease and also testing the drug combinations in different models of childhood neuroblastoma.

"Because DFMO has been shown to be quite safe and is approved for use in humans, we would hope that we can proceed rapidly to clinical trials," said Professor Haber.

Researchers at CCIA, in partnership with the Sydney Childrens Hospital, Randwick and the Childrens Hospital of Philadelphia, U.S.A., are in the final planning stages of progressing these findings into clinical trial.

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