Development of new treatments for children with high-risk neuroblastoma

26 June 2014
Professor Louis Chesler, The Institute of Cancer Research, London

Neuroblastoma has a high-risk form that, despite intensive treatment, has a very poor outlook. The aim of this project is to develop new treatments that kill neuroblastoma cells by targeting the specific gene associated with this high-risk disease but, importantly, do not harm normal cells. This could improve survival in young patients whilst reducing the risk of treatment-related harm.

Amount of grant: £249,675 | Date of award: June 2014


Neuroblastoma, a cancer that originates in developing nerve cells, is the second most common solid tumour to occur in children, affecting up to 100 children every year in the UK. Most of these children are under the age of five years, with children under the age of one at greatest risk of developing the disease.

Around 40 per cent of children diagnosed with neuroblastoma have a high-risk form that is essentially incurable using conventional treatments (chemotherapy, radiotherapy and surgery).

High-risk neuroblastoma is associated with abnormalities of a gene called MYCN. Even with very intensive therapies, the majority of children with MYCN neuroblastoma still relapse following treatment and die.

Multiple duplication of the MYCN gene in neuroblastoma is the single most powerful indicator of poor outcome and gives rise to tumours that are very aggressive. The MYCN protein made by the gene has such a powerful cancer-causing effect that neuroblastoma cells become “addicted” to it and cannot survive if it is not present.

In this project, Professor Chesler is focusing on the development of potent and selective drugs that can target MYCN more effectively and therefore improve outcome for children with this form of the disease.

The team will develop new drugs that kill neuroblastoma cells by specifically interfering with the interaction between MYCN and a protein called Aurora-A kinase, which protects MYCN from being broken down.

About the research team

Professor Chesler is the Leader of the Paediatric Solid Tumour Biology and Therapeutics Team at the Institute of Cancer Research. His lab has a great deal of experience in the pre-clinical development of drugs targeted against MYCN, which has led to the development of new therapies.

Collaborators Professor Martin Eilers, at the University of Wurzburg in Germany, and Dr Richard Bayliss, at the University of Leicester, are working closely with the ICR team to define the MYCN biology and protein structures that will allow them to develop better drugs.

Collectively, they represent a unique grouping of laboratories with expertise in this field of research, a strong publication record as well as excellent preliminary data.

The CRUK Cancer Therapeutics Unit at ICR is the largest academic cancer drug discovery and development group worldwide and has discovered 16 anti-cancer drug candidates in the last 10 years. Thus the team has access to all of the research and pre-clinical tools required to carry out the proposed work.

What difference will this project make?

Outstanding proposal, highly novel, high translational potential – must fund.
External reviewer
Progress in the treatment of high-risk neuroblastoma has been limited and, even with very intensive therapies, the majority of patients still die. For the lucky children who beat the disease, survival can come at a high cost. Two thirds of children who survive cancer face at least one chronic health condition and one third of survivors face a late-effect that is classified as severe or life-threatening. This can include heart damage, second cancers and lung damage.

The potential clinical benefits of the new drug treatments being developed in this project are significant if they not only impact survival but also reduce side-effects and late-effects.

It is also predicted that these new drugs will have a place treating paediatric brain tumours, and rhabdomyosarcomas that are also driven by the MYCN gene.

Read more: Neuroblastoma | Treating childhood cancer | Side effects of treatment


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