Novel treatment against childhood cancer neuroblastoma
Neuroblastoma is a childhood cancer derived from the sympathetic nervous system. Treatment of children with high-risk neuroblastoma remains largely unsuccessful, because of metastasis and treatment resistance, and is a serious clinical problem. There is therefore an urgent need for development of novel treatment for these children. One major obstacle in translational cancer research has been the lack of predictive preclinical models that faithfully represent tumors occurring in patients. Consequently, many therapeutic approaches based on these in vivo models have failed in clinical trials. We have recently established and characterized the first neuroblastoma orthotopic patient-derived xenografts (PDXs) by implanting patient-derived tumor explants into mice. These PDXs display invasive growth, spontaneous metastasis, and recapitulate the histology, protein marker expression, and clinically important gene copy number changes of the original tumors. Our goal is to use neuroblastoma PDXs to comprehensively characterize and target neuroblastoma metastases and treatment resistance. We combine next generation sequencing, in vitro drug testing, cell- and molecular biology techniques, in vivo drug testing and advanced in vivo imaging to understand and target metastatic and treatment resistant tumors. Novel strategies for inhibiting aggressive neuroblastoma while minimizing toxicity are expected to increase survival of neuroblastoma patients, for whom prognosis is currently poor.