Why do children get cancer? The sequential acquisition of oncogenic mutations is believed to be rate limiting for tumor initiation, providing an explanation why aging is the biggest risk factor for developing cancer. Paradoxically, the incidence of some cancers, such as leukemia and brain tumors, peaks early in life and decreases before rising again with age. We aim to clarify this paradox and by doing so obtain insight into the molecular and cellular mechanism underlying cancer initiation. Also, some cildhood cancers can spontaneously regress, such as transient myeloproliferative disorder in newborns with Down syndrome. We aim to understand what factors contribute to this spontaneous regression and examine if this knowledge can be used to treat childhood cancers.
Cancer survivors have an increased risk of developing second malignancies as a consequence of their lifesaving treatment. In fact, second malignancies are a major cause for long-term mortality of childhood cancer survivors. We aim to determine the genotoxic effects of cancer treatment on normal stem cells and identify the rate-limiting steps underlying the genesis of second malignancies in cancer survivors. With this knowlegde, we may be able to develop preventive strategies, such as adapted treatment for the first cancer and/or intensive monitoring after remission.