.tmb-propic-md.jpg?Culture=en&sfvrsn=c25d2b2f_9 "Professor Louis Chesler (Profile pic)")
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Scientists from The Institute of Cancer Research, London, will be part of a team of international researchers who have secured funding to study the genetic secrets of childhood cancer neuroblastoma.
The £1.5million funding boost from Cancer Research UK (CRUK) has raised hopes that the project, led by scientists at the University of Sheffield, alongside colleagues from The Institute of Cancer Research (ICR), Kings College London, The St. Anna Children's Cancer Research Institute, Vienna and the Medical University of Vienna, will lead to new treatments for the disease.
Neuroblastoma is a type of cancer that develops from the neural crest cells, which are left over from a baby’s development in the womb. The disease affects around 100 children a year in the UK and most commonly occurs in those under the age of five.
Challenges in treating neuroblastoma
A major challenge in treating high-risk neuroblastoma is its complex genetic makeup, which contributes to its aggressive nature and unpredictable response to treatment.
Neuroblastoma often involves changes in the number of copies of certain chromosomes known as Copy Number Alterations (CNAs). Some genes might have too many copies, while others might have too few.
Another key driver is the MYCN oncogene, which normally helps cells develop but becomes ‘overactive’ in neuroblastoma, causing cells to grow too much and too quickly.
The project will focus on studying how these genetic changes disrupt the normal development of neural crest cells. By meticulously tracking the impact of CNAs and MYCN overactivation on these cells, the researchers hope to gain crucial insights into the cancer's origins and the factors that contribute to its heterogeneity (the presence of diverse cell types within a single tumour).
The teams will use human stem cells to produce ‘mutant neural crest cells’, carrying the same genetic errors as those seen in neuroblastoma.
Investigating how altered cells respond to treatment
This will allow the researchers to study how these genetic errors affect the cells as they grow and develop into cancer. They will also investigate how these genetically altered cells respond to standard chemotherapy and try to understand how the disease evades the drug and identify potential vulnerabilities that could be exploited by new therapies.
The ICR team will include Professor Louis Chesler, Professor of Paediatric Cancer Biology at The Institute of Cancer Research, London, and Consultant in Paediatric Oncology at The Royal Marsden NHS Foundation Trust, along with Dr Sally George, Group Leader of the Developmental Oncology group, Dr Alejandra Bruna, Group Leader of the Preclinical Modelling of Paediatric Cancer Evolution team and Dr Evon Poon, Senior Scientist.
'This research is likely to provide valuable insights into potential therapeutic targets for treating neuroblastoma'
Professor Louis Chesler, Professor of Paediatric Cancer Biology at The Institute of Cancer Research, London, and Consultant in Paediatric Oncology at The Royal Marsden NHS Foundation Trust, said:
“Cancers in children cause over one in five deaths in children under the age of 14 in the UK. Many of these cancers start in the womb, before the child is even born. Unlike adults, children’s cancers are caused by a relatively small number of genetic mutations.
“The main goal of this project is to understand how these genetic errors disrupt the normal development of embryonic cells and promote the formation of tumours. Although this is primarily a research project, the findings are likely to provide valuable insights into potential therapeutic targets for treating children with aggressive neuroblastoma.”
Dr Anestis Tsakiridis, group leader at the Centre for Stem Cell Biology at the University of Sheffield, said:
“By examining how the complex genetic code of neuroblastoma converts normal embryonic neural crest cells into their cancerous counterparts, we aim to identify new therapeutic targets for treatment - potentially leading to reduced drug resistances, preventing relapses and saving lives.”