Neuroblastoma is a pediatric tumor arising from progenitors of the peripheral nervous system. Half of the patients present with an aggressive form that is difficult to treat resulting in poor survival. Treatment of aggressive neuroblastoma is very intensive with many toxic side effects even in the long term for the patients who survive the disease. In this study, the main goal is to explore the therapeutic potential of pharmacological targeting the replicative stress signaling pathway in high-risk neuroblastoma. We will particularly focus here on new generation drugs that can induce synergistic effects in combination. Extensive preclinical work in vitro and in vivo using mouse models will form the basis to initiate a phase 1 clinical trial.