SUMMARY/ABSTRACT High-risk neuroblastoma (NB) remains a therapeutic challenge with expected 5-year overall survival of no more than 50%, despite advances in the past two decades with myeloablative therapy, differentiating therapy and immunologic and genetically targeted therapies. Core B is the translational linchpin of our multi-disciplinary and multi-institutional P01, Discovering and Exploiting Mechanisms of Neuroblastoma (NB) Therapy Resistance. The goal of Core B will be enabled by the well-established New Approaches to Neuroblastoma Therapy (NANT) consortium, and has the overall objective of capitalizing on our clinical trials expertise and infrastructure to support the translation of new therapies with demonstrated pre-clinical activity against relapsed and refractory (resistant) NB developed in Projects 1-5 into clinical care, in order to ultimately improve the poor survival of children with high-risk NB. The three specific aims of this Core are: 1) to provide the clinical expertise for translation of preclinical work from Projects 1-5 collaboration with the statistical Core and the Project investigators; 2) to provide the established and adaptable infrastructure for rapid implementation into early phase clinical trials; 3) provide the infrastructure for embedded correlative studies, and a unique biorepository of highly annotated tumor tissues, bone marrow, blood, and radiologic images obtained from resistant NB patients, with genomic and pathologic analysis. Core B will obtain safety, mechanistic, and response data from phase 1/2 trials to support promising therapies from Projects 1-5 to be tested in larger national and international Phase 2 and 3 trials. This highly integrated P01 will allow rapid translation from laboratory to patients, with individualized treatment, utilizing more precise biomarkers of response. Thus, Core B will contribute substantively to the overall success of the Program and ultimately improved high-risk NB patient outcome.