Major NH&MRC grant will fund multidisciplinary research to improve the treatment of neuroblastoma

07/26/05

Significant funding from the NH&MRC will enable researchers at Children's Cancer Institute Australia (CCIA) for Medical Research to make progress on the treatment of one the most aggressive, drug-resistant childhood cancers--neuroblastoma--over the next five years.

With a comprehensive understanding of the biology of neuroblastoma, three senior CCIA researchers and their teams are determined to improve the survival rates for children with this disease through the development of new, safer treatments and possibly even prevent the disease in future.

In mid-July the NH&MRC announced a $4.7 million grant was being awarded to a team comprising Prof Michelle Haber, Head of Experimental Therapeutics and Executive Director of CCIA, A/Prof Murray Norris, Head of Molecular Diagnostics and Deputy Director of CCIA and A/Prof Glenn Marshall, Head of the Molecular Carcinogenesis Program at CCIA and Director of the Centre for Children's Cancer and Blood Disorders at Sydney Children's Hospital to improve the treatment of children with neuroblastoma.

The three principal investigators will be building on the fundamental research they have carried out on neuroblastoma for over a decade. They will be able to expand their research using laboratory models of neuroblastoma which closely reflect the human disease, and which are considered among the best in the world.

Treatment of neuroblastoma, the most common solid tumour in children under five, has not improved much over the last thirty years. It remains an aggressive, debilitating and life-threatening cancer. Mortality is often as high as 60% because most children present with advanced disease that responds poorly to conventional chemotherapy and other forms of treatment. Neuroblastoma has both intrinsic and acquired drug resistance.

"With the additional resources we expect to make great progress in the study of neuroblastoma, a disease that results in about 15% of deaths from childhood cancer," said Prof Haber.

"Five year funding gives us a tremendous opportunity to answer the big questions in child cancer: how does it start and how can we improve treatment?" added co- investigator A/Prof Glenn Marshall, who is also a Paediatric Haematologist and Oncologist, and has been treating children with this disease for almost fifteen years.

The grant will fund a comprehensive research plan that involves tackling the disease systematically on several fronts to:

  • acquire a thorough understanding of the molecular basis of neuroblastoma by identifying key genes and pathways associated with its initiation and perpetuation;
  • understand the failure of specific biochemical signalling (retinoid) in defective cell differentiation;
  • identify cancer-specific genes in neuroblastoma that are good candidates for the development of molecular targeted gene therapy;
  • identify compounds with the ability to inhibit target genes; and
  • translate novel anticancer therapies into clinical applications.

The funding will enable researchers to expand their groundbreaking work on the role of Multidrug Resistance-associated protein-1 (MRP1), the oncogene MYCN and the retinoic acid receptor. Retinoic acid is a Vitamin A derivative and is used in the treatment of neuroblastoma.

Recent work has shown that two types of cellular events lead to the development of neuroblastoma tumour formation. One mechanism involves the activation of the oncogene MYCN while the other involves defective differentiation of neuroblasts (embryonic nervous tissue). Differentiation is the process whereby cells assume a special function or activity.

"Because many types of childhood cancer arise in embryonal tissue, our findings could have great relevance for other cancers including medulloblastoma, Wilm's tumour, acute lymphoblastic leukaemia and Ewings' sarcoma." said A/Prof Murray Norris.

Source: Eurekalert & others

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