Understanding why some children with neuroblastoma have worse survival or respond badly to treatment

This project aims to improve survival for patients with high-risk neuroblastoma and to reduce the toxicity (side effects) of existing interventions (i.e provide kinder treatments).

Neuroblastoma accounts for 6% of all childhood cancer but has one of the lowest survival rates. High-risk patients are treated with multiple chemo- and radiotherapy regimes that result in harsh toxic side effects. Despite this, in many cases there is limited response and the 5 year survival rate is just 40-50%. The need for new treatments for high-risk neuroblastoma is therefore desperate.

We have demonstrated that a biological pathway called the “Fanconi anaemia” (FA) pathway is present at higher levels in some patients with neuroblastoma and that these patients have more severe disease and die earlier than patients with low levels of the FA pathway. We want to understand why the FA pathway is causing this effect and will test the ability of novel drugs that prevent the FA pathway from working (FA inhibitors) to specifically kill neuroblastoma cells and to specifically increase the response of neuroblastoma to existing drug therapies, thus improving survival and providing more targeted, kinder therapies with fewer side effects.

We will use a range of neuroblastoma cells grown in the laboratory to examine how repair of damaged DNA and cell growth (replication) is affected by the FA pathway. We will use commercially available FA inhibitors alone and in combination with standard chemotherapies to prove the pathway is a valid therapeutic target and pave the way for development of drugs to use in children with neuroblastoma.

This project will increase our understanding of why some children with neuroblastoma have worse survival and/or respond badly to treatment. Significantly it may also provide targeted treatments for high-risk hard to treat neuroblastoma, thus allowing improved survival and kinder treatments for patients, reducing short term and long term side effects of therapy.