Biomarkers allow doctors to match therapy ...(of the MYCN oncogene has a particularly ...)

Date:4/13/2008

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.

Researchers observed 209 patients with untreated neuroblastoma. As expected, they 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 tested whether inhibiting ODC1 activity with difluoromethylornithine (DFMO), a proven ODC1 inhibitor, would improve treatment of neuroblastoma, when used in combination with conventional chemotherapeutic drugs. They found that the combined

DFMO/chemotherapeutic drug therapy prolonged tumor-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, said Haber.

The next step would 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 for use in humans, we would hope that we can proceed rapidly to clinical trials, said Haber.

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Contact: Staci Vernick Goldberg Staci.goldberg@aacr.org 267-646-0616 American Association for Cancer Research Source:Eurekalert

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