Neuroblastoma is the most common extracranial solid tumor in children. Since its first description some 150 years ago, its enigmatic clinical presentation has challenged clinicians and fascinated basic researchers. This article presents an overview of the key clinical features of neuroblastoma and current therapeutic approaches. It also highlights how our understanding of sympathoadrenal developmental biology, coupled with transcriptome analyses, next-generation sequencing, and genome-wide association and epigenetic studies, has illuminated critical signal transduction pathways involved in neuroblastoma tumorigenesis and identified therapeutically tractable targets for clinical development.

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