Our research focuses on investigating the underlying molecular defects giving rise to a rare but important subgroup of human cancers, and to translate advanced understanding into novel therapies.
Childhood cancers are a rare but important subgroup of human cancers that have been pivotal in unravelling some of the critical genetic events in oncogenesis; in particular childhood tumours were the first human cancers in which tumour suppressor genes were discovered. These cancers begin developing before a child is born, arising from immature cells that give rise to cancers which are unique to children, such as Wilms' tumour (a kidney cancer) and neuroblastoma (a cancer of the sympathetic nervous system).
The overall survival rate for childhood cancers has increased dramatically since the 1960s, so that more than 75% of children with cancer now survive. However, there are certain cancers, such as advanced neuroblastomas, which still have a very poor prognosis and for those children who are cured, there can serious long-term side effects from current therapies.
Research in the school, that is being undertaken by Keith Brown, Karim Malik and Stefan Roberts focuses on investigating the underlying molecular defects that give rise to children's cancers, with the aim of translating these findings into novel therapies. Our research has concentrated particularly on Wilms' tumour and neuroblastoma. Research into the role of the WT1 gene in Wilms' tumour has led to important advances in understanding how epigenetic defects play a role in the development of paediatric cancers. This has led in recent years to genome-wide investigations of the role of epigenetic defects, such as DNA methylation and histone modifications (see epigenetics and cancer), which are reversible modulators of gene expression and thus are tractable targets for therapeutic interventions. Research in Nuclear Dynamics Laboratory (Abder Kaidi) aims to applying synthetic lethality strategies for targeting chromatin regulators in childhood cancers associated with replicative and/or genotoxic stresses.
Research within the school into childhood cancers, including childhood leukaemia, is also carried out by the cancer stem cells group.