Neuroblastoma (NB) is the most common solid tumor outside the brain of infants and very young children. The aggressive forms of neuroblastoma are often accompanied by an increased resistance to current chemotherapies due to defects in the molecular mechanisms that normally leads to the death of cancer cells. Therefore, the challenge is to find new molecular mechanisms to kill the cancer cells. Recently, we discovered a new approach to kill aggressive therapy-resistant neuroblastoma in mice by triggering a sort of biological rusting in cancer cells called ferroptosis. Ferroptosis is an iron-driven oxidation reaction of the membranes of cancer cells, which quickly kills the cells. By using nanoparticles, we were able to minimize the side effects of treatment and enhanced tumor targeting. However, to get tumor regression without relapse using a nanomedicinal approach, it is needed to further improve and validate the efficacy of ferroptosis targeting in neuroblastoma. In this project, we will use different genetic and pharmacological approaches to improve the therapeutic applicability of ferroptosis in neuroblastoma. To this end, we will use genomically well-characterized patient-derived neuroblastoma models to identify potent ferroptosis triggers in order to achieve more effective suppression of tumor growth and avoid relapses.