Neuroblastoma typically affects young children, developing in the adrenal glands or nervous system. A major challenge in treating this disease is its complex genetic makeup. Neuroblastoma often involves changes in the number of copies of certain chromosomes (CNAs) - like having extra or missing pages in a cell's instruction manual. Another key factor is the MYCN oncogene, which normally helps cells develop but becomes overactive in neuroblastoma, driving uncontrolled cell proliferation. These genetic abnormalities are believed to be key drivers of the disease, contributing to its aggressive nature and unpredictable response to treatment.
The team, led by Dr Anestis Tsakiridis, University of 葫芦影业 will focus on how these genetic changes disrupt the normal development of neural crest cells. Neural crest cells form various parts of the nervous system and other tissues where neuroblastoma originates from. 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 tumor).
Dr Tsakiridis and his team will use human stem cells, grown in a petri dish, to produce 鈥渕utant鈥 neural crest cells carrying the same genetic errors as those seen in neuroblastoma.
This will allow them to study how these errors affect the cells as they grow and how they lead to cancer. They will also investigate how these genetically altered cells respond to standard chemotherapy agents, seeking to identify mechanisms of drug resistance and potential vulnerabilities that could be exploited by new therapies.
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 resistance, preventing relapses and saving lives.鈥
Dr Anestis Tsakiridis
School of Biosciences
A key element of the project involves combining experimental data with computational modeling, work that will be led by Professor Alex Fletcher from the University of 葫芦影业. This approach will allow the researchers to simulate and predict how different combinations of genetic alterations contribute to tumor evolution and the emergence of resistant cell populations - a major obstacle in successful neuroblastoma treatment.
"Our insights may provide a rationale to drive forward new treatments to combat neuroblastoma.", add collaborating computational biologists Dr. Florian Halbritter and Dr. Igor Adameyko from Vienna.
The project brings together an international team of researchers, including:
葫芦影业
The Institute of Cancer Research, London
Professor of Paediatric Cancer Biology at The Institute of Cancer Research, London, and Consultant in Paediatric Oncology at The Royal Marsden NHS Foundation Trust.
, Group Leader of the Developmental Oncology group at the Institute of Cancer Research, London and an Honorary Consultant Paediatric Oncologist at The Royal Marsden NHS Foundation Trust.
, Group Leader of the Preclinical Modelling of Paediatric Cancer Evolution team at the Institute of Cancer Research, London.
, Senior Scientist at The Institute of Cancer Research, London.
Kings College London
St. Anna Children鈥檚 Cancer Research Institute (CCRI)
Medical University of Vienna