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First Stage Study Finds Potential New Drugs For Neuroblastoma

Scientists at The Institute of Cancer Research, London have made a step towards new, targeted drugs for children with the highestrisk form of a called neuroblastoma.

In a preclinical study, published in journal Cancer Cell , researchers successfully used two potential drugs to target cancerous neuroblastoma cells with an overactive gene called . The gene plays a major role in most cases of aggressive and treatmentresistant neuroblastoma in children, as well as in some adult cancers.

In the study, scientists showed that two drugs, from a class called Aurora kinase inhibitors, disrupted growth in laboratory cultures of human cancer cells with overactive MYCN. They then showed that the drugs were effective against neuroblastoma tumours in mice with tumours caused by increased activity of MYCN. The drugs had a significant therapeutic effect against rapidly growing, aggressive neuroblastomas, as a result of the destruction of NMyc, the protein produced by the MYCN gene.

The study was funded by the charity Christopher’s Smile, the Neuroblastoma Society, the Sparks Medical Charity, and the Medical Research Council.

Neuroblastoma is a cancer of developing nervous tissue which almost always begins very early in life. Usually causing tumours to develop in the chest or abdomen, it affects around 100 children in the UK each year (1), accounting for about 6 per cent of childhood cancers. It disproportionately affects very young children, making up more than one in five cancers diagnosed in infants under one year of age (2). Around half of children with neuroblastoma have a highrisk type which is resistant to all current treatments. Almost all highrisk patients have overactive MYCN.

The drugs are called MLN8054 and MLN8237. They work by causing the breakdown of the protein produced by the MYCN gene, called NMyc, in cancer cells. Overproduction of NMyc drives other, procancer genes to produce proteins which make tumours particularly resistant to current treatments.

MYCN has been known to scientists as a potentially important cancer target, but after many early, unsuccessful attempts it was widely considered to be undruggable. In this study, scientists targeted MYCN in an indirect way: MLN8054 and MLN8237 prevent NMyc from binding to a stabilising protein called AuroraA. Without this interaction, NMyc is targeted for destruction in cancer cells.

Dr Louis Chesler, Head of the Paediatric Solid Tumour Biology and Therapeutics team at The Institute of Cancer Research, who coled the study, said:

“Highrisk neuroblastoma is very frequently fatal, even after the most intensive possible treatment with our most powerful drugs. It’s essential to find more effective and curative therapies.

“Our small but promising study has made a step forwards by finding a practical way to target the MYCN cancercausing protein in children with this devastating disease. This has been a longsought after, but so far unachieved goal.

“However, much work remains to establish that MYCN targeted drugs are safe and effective for children in the clinic. Our next step will be to trial these drugs in children who aren’t responding to conventional treatments, and those whose disease has relapsed.

“We are very hopeful that our work will help towards a new clinical strategy to directly target cancercausing genes in childhood cancer, using drugs designed specifically for children.”

Karen Capel, cofounder and trustee of Christopher’s Smile, which cofunded the study, said:

“Christopher’s Smile is pleased to fund cutting edge research which utilises targeted agents to treat cancers such as high risk neuroblastoma. Our strategy is to fund projects that will enable personalised medicine for children with cancer to save the 25 per cent of children who do not survive their disease.”

Dr Guy Blanchard, Research Trustee at The Neuroblastoma Society, which cofunded the study, said:

“We welcome this exciting new development in the hunt for a treatment for MYCNamplified neuroblastoma, one of the most aggressive and untreatable forms of the disease. We congratulate Dr Chesler and hope that AuroraA inhibitors can be brought to trial as soon as is reasonably practicable.”

John Shanley, chief executive of Sparks, which cofunded the study, said:

“Funding research that helps prevent, diagnose, treat and cure conditions affecting the health of children is at the heart of what Sparks does.

“Neuroblastoma is a very unpredictable form of childhood cancer which can be difficult to treat, many of the current treatments are not effective and aggressive therapies can cause serious side effects for the children.

“We welcome this new research, which should help researchers to develop more effective, targeted therapies meaning that the harsh side effects of more aggressive treatments are minimised.”


1. University of Oxford Childhood Cancer Research Group: Childhood Cancer Registrations, Great Britain, 19712005 (20015). Accessed online 19 June 2013.

2. Cancer Research UK Childhood cancer incidence statistics: 200810. Accessed online 18 June 2012.

Source: The Institute of Cancer Research, London