19 September, 2011
A team of scientists at Children's Cancer Institute Australia (CCIA) has published the results of a ground breaking study that has uncovered a new role for a set of genes involved in one of the deadliest forms of childhood cancers, Neuroblastoma.
“Neuroblastoma is the commonest solid tumour in young children,” explains Professor Michelle Haber, AM, Executive Director of CCIA. “It's often diagnosed late when the tumour has already spread and despite aggressive treatment regimens, outcomes remain poor for children with advanced disease. New treatment approaches are urgently needed, and that's why this finding from our Institute is of such importance.”
“This discovery was a big surprise for us,” says Dr Michelle Henderson, the lead author on the study, which has been published in the prestigious Journal of the National Cancer Institute in the US.
The study involves members of a gene family known as the Multidrug Transporter genes, which were first shown by the CCIA research team some years ago to predict for very poor outcome in children with neuroblastoma, when present at high levels in the tumour cells of the child. The association with poor outcome was believed to be due to the ability of these transporters to pump chemotherapy drugs out of the cancer cell. This new study, however, shows that these transporters have a far more complex role in tumour growth than ever suspected, and can actually drive the malignant behaviour of the tumour cells.
“We know that these transporters give cancer cells the ability to escape the effects of chemotherapy by actually pumping out the anti-cancer drugs before they can kill the cells. We knew from our earlier studies that if a child's tumour possessed high levels of these transporter genes, then the child was likely to do very badly.
“But we suspected there was more to these transporter genese than just causing resistance to chemotherapy and that's what this study was about,” explains Dr Henderson.
“We had identified many patients with high levels of transporter genes in their tumours who had not been treated with chemotherapy drugs that these transporters could pump out, and yet they still fared much worse than children with low transporter levels in their tumours. So they seemed to predict a bad result even when no drugs were administered. To cut a long story short, we've found, unexpectedly, that these so called ABC transporter genes can directly influence the growth and invasive capacity of the cancer cells. They appear to be fundamental to the cancer itself.
“The implications of these findings are profound,” says Professor Murray Norris, Deputy Director and Program leader at CCIA, and senior author of the study. “Our study has completely changed the understanding of this important area of cancer biology. Up to now we simply did not have the full picture. Unravelling the mechanisms by which these genes assist tumour growth will allow us to identify new drug targets and ultimately develop a more effective approach to inhibit their action.”
“Neuroblastoma isn't the only difficult to treat cancer where these ABC transporter genes are found,” says Professor Haber, who was joint first author of the study. “We have evidence suggesting that our findings have relevance to other adult cancers as well. We pride ourselves at CCIA on making laboratory findings that can be rapidly translated to the clinic, and we are excited about the potential new treatment approaches for childhood and adult cancer that these new findings suggest.”
PR & Communications, Children's Cancer Institute Australia
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