CORE B SUMMARY/ABSTRACT High-risk neuroblastoma (NB) remains a therapeutic challenge with nearly 50% of patients experiencing relapse after aggressive multi-modal therapy including intensive induction chemotherapy, surgery, myeloablative chemotherapy, radiation therapy, differentiating therapy and immunotherapy. Survival for those patients whose tumors relapse or are refractory to upfront therapy (resistant NB) remains dismal; however, identification of tractable molecular aberrations and immunotherapy combinations (chemoimmunotherapy) provide novel approaches to address this urgent issue. Core B will provide the needed clinical and statistical expertise, and an infrastructure derived from 23 years of experience, to develop and conduct the clinical trials to exploit molecular and immunologic therapeutic vulnerabilities identified by Projects 1-4. We will leverage the expertise of the well-established New Approaches to Neuroblastoma Therapy (NANT) consortium to ensure the efficient translation of laboratory research into paradigm-changing therapy for high-risk NB. NANT, founded in 2000, has conducted 34 therapeutic and biology/biomarkers trials, to date enrolled 1426 patients with resistant NB, and informed ongoing NCI-funded national clinical trials that will enable New Drug Applications for two novel high-risk NB therapeutics. The 17 international highly motivated children’s cancer centers that comprise NANT have extensive NB-specific translational expertise with the infrastructure to conduct complex clinical trials. NANT has innovative statistical designs and correlative biology studies embedded into all clinical trials integrated with the original laboratory research, a comprehensive tissue bank focused on resistant NB providing a unique resource of annotated patient data, resistant tumor tissues, bone marrow, blood, and electronic images for scientific studies in the P01 Projects. The overall objective of Core B will be to leverage NANT consortium’s clinical trial, biostatistical and operational infrastructure to accelerate the translation of new therapies that target therapeutic vulnerabilities of resistant NB uncovered by Projects 1-4. The long-term goal of this Core is to enable paradigm-shifting changes in high-risk NB clinical care that will ultimately dramatically improve the survival probability with less toxicity. Core B will provide the mechanisms to obtain and provide resistant tumor samples, annotated with the NANT clinical database and electronic imaging repository, detailed molecular profiling, and data from biologic correlative studies. These cumulative data will be used in this Program to inform selection of specific therapies and/or to develop predictive biomarkers of response. Core B is essential to the translational mission of the Program and has served as the major pipeline for Phase 3 testing in newly diagnosed high-risk NB patients.