This project studies the role of clusterin gene in the development of neuroblastoma and in chemotherapeutic drug resistance. • Neuroblastoma – v aggressive tumour of the nervous system, accounts for 15% cancer deaths in children. 75% neuroblastomas occur in children under 5 years. Leading cause of cancer deaths in 1-4 year olds • Clusterin is a gene – produces an “enigmatic” protein that may be involved in a wide range of cell functions – cell death/cell immunity/cell transformation • NF-kB is a transcripton factor (transfers info contained in the genetic code from DNA to RNA) - often activated in cancer and very important in tumour cell processes such as invasion and metastasis (spread) o Clusterin is a natural suppressor of NF-kB activity. Stress signals and exposure to chemotherapeutic drugs can induce clusterin in normal cells but expression of clusterin is altered in human cancer. Research has shown that: • Its absence may favour tumour development • It may cause enhanced survival or killing of neuroblastoma cells • clusterin can also suppress drug killing of neuroblastoma cells Research project investigates: • whether the presence or absence of the clusterin gene enhances or suppresses neuroblastoma development (ie looks at the neuroblastoma development in mice with and without the clusterin gene) • And if cancer treatment drugs will be more/less effective in absence of clusterin in the body. Outcomes (within 5 year time frame) • greater understanding of the role of clusterin in neuroblastoma • clarification of drug response, eventual improved drug treatment • Overall – aim to establish new criteria for patients treatment and improved predictions of patient survival probability INSTITUTE OF CHILD HEALTH £146,647 over 3 years Start date: Feb 2006 – Jan 2009