Oz researchers identify potential new target for treatment of neuroblastomaApril 14th, 2008 - 4:27 pm ICT by admin
Washington, April 14 (ANI): Researchers in Australia have identified a potential new target for treatment of neuroblastoma, the most common solid tumour among young children.
In the study, researchers found that inhibiting the production of ornithine decarboxylase ODC1 - a gene driven by the MYCN oncogene that is a powerful predictor of death from this disease - delayed or prevented the development of neuroblastoma in a clinically relevant animal model.
This suggested that suppressing ODC1 could be target for treating this cancer.
This disease, particularly in patients whose tumors carry multiple copies of the MYCN oncogene, has a particularly poor prognosis and new therapies are urgently needed, said Michelle Haber, Ph.D., professor and executive director of Childrens Cancer Institute Australia for Medical Research in Sydney, Australia.
Our findings suggest that MYCN-driven over-expression of ODC1 in this disease, or genetic variations associated with increased expression of the gene, contribute to the aggressive biology of this tumor, and that inhibition of this gene may lead to an important new therapeutic avenue for this disease, Haber added.
For the study, researchers examined 209 patients with untreated neuroblastoma.
Researchers confirmed that older age, advanced stage and MYCN amplification were all associated with highly aggressive disease and poor clinical outcomes.
In a subsequent animal study, researchers examined whether inhibiting ODC1 activity with difluoromethylornithine (DFMO), a proven ODC1 inhibitor, would improve treatment of neuroblastoma, when used in combination with conventional chemotherapeutic drugs.
The test showed that the combined DFMO/chemotherapeutic drug therapy prolonged tumour-free survival by comparison with chemotherapeutic drugs alone, suggesting that targeting this oncogene for suppression is a potentially valuable therapeutic approach.
We could actually delay, and in some cases block, neuroblastoma formation in our transgenic MYCN mouse model by continuous exposure to DFMO either from birth or following weaning, and found that this delay was associated with depletion of tumoral polyamines, Haber said.
Because DFMO has been shown to be quite safe for use in humans, we would hope that we can proceed rapidly to clinical trials, Haber added. (ANI)
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Tags: aggressive disease, amplification, animal model, animal study, chemotherapeutic drugs, childrens cancer institute, clinical outcomes, decarboxylase, free survival, genetic variations, inhibition, medical research, neuroblastoma, oncogene, poor prognosis, study researchers, sydney australia, target, therapeutic approach, tumour