While survival rates in paediatric cancers have increased significantly the past decades, for certain entities there is still a high rate of treatment failure such as for children with high risk neuroblastomas and relapsed T-cell acute lymphoblastic leukemias (T-ALL). Furthermore, treatment for high risk paediatric cancers is harsh and associated with severe long term side effects including secondary cancer at later age. Therefore, the search for more effective and less toxic therapeutic options remains one of the most challenging tasks in cancer research. Our lab has made a new recent discovery concerning the PHF6 gene that we previously identified in T-ALL. For the first time, we have strong evidence for a role in the control of genes normally implicated in the regulation of cell identity, genes which are often perturbed in cancer cells. We will first study this new mechanism in further detail using the newest techniques and in vivo modelling in zebrafish. Next, we also have preliminary data suggesting that a combination of two novel drugs allows to target PHF6 as part of a broader regulatory network controlled by the FOXM1 transcription factor. As such, we will further expand these promising preliminary drugging data in a large panel of neuroblastoma and T-ALL cell lines and animal models for pre-clinical testing prior to moving to patient clinical trials.