Neuroblastoma (NB) is the second most common childhood cancer. It develops from the sympathetic nervous system and the majority of children with high-risk disease die from cancer relapse despite intensive treatment. Changes in two cancer-causing genes, MYCN and ALK, are closely associated with poor outcome. The role of MYCN in causing high-risk NB is well recognised, but ALK was only recently identified. It is unknown whether ALK can cause NB alone, or requires an interaction with MYCN. Clinical evidence suggests that patients with concurrent abnormalities in both ALK and MYCN genes have uniquely aggressive disease and very poor survival. Our laboratory has developed the first genetically engineered model of NB in which both MYCN and ALK are abnormal. As in patients, tumours are aggressive and survival is poor. I hypothesise that ALK cooperates with MYCN to cause NB and will use our model to establish how MYCN and ALK cooperate and to evaluate whether drugs that attack ALK, Mycn or both proteins are needed to stop tumour growth. If my work succeeds, we will identify new, molecularly-targeted drugs that could be utilised in clinical trials for patients with relapsing NB. Currently these patients have no options for treatment.